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Immunbiologie von dendritischen Zellen / Immunobiology of dendritic cells

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(Ausgewählte Publikationen / list of selected publications)

a.o.Univ.-Prof. Dr.phil. Christine Heufler Tiefenthaler, Assoz.-Prof. Dr.rer.nat. Patrizia Stoitzner, Dr.rer.nat. Nikolaus Romani (Professor für Experimentelle Dermatologie i.R.) und Mitarbeiterinnen und Mitarbeiter

Weitere Informationen über das Laboratory for Langerhans Cell Research von Prof. Stoitzner 

 

Dendritische Zellen sind Leukozyten, die zur Stimulation von T Zell-abhängigen Immunantworten hochspezialisiert sind. Sie sind entscheidend beteiligt an der Aktivierung von Helfer T Lymphozyten, an der Steuerung der Zytokinmuster der entstehenden Helfer T Lymphozyten, an der Aktivierung und Entwicklung von zytotoxischen Killer T Lymphozyten, an der Produktion von Antikörpern, sowie an der Aktivierung von Makrophagen. Dendritische Zellen sind die einzigen Zellen des Organismus, welche primäre Immunantworten einleiten können. Sie stehen also kritisch am Beginn jeder primären Immunreaktion. Die dendritischen Zellen der Epidermis sind die in der dermatologischen Forschung schon lange bekannten Langerhanszellen.
Die Forschung über dendritische Zellen hat an der Hautklinik bereits eine mehr als 25-jährige Tradition. Sie hat ihre Wurzeln in den klassischen Pionierarbeiten über Langerhanszellen der Professoren Klaus Wolff, Georg Stingl und Peter Fritsch. Sie wurde massiv ausgebaut und verankert unter Professor Gerold Schuler. Eine dauerhafte, aktive Beziehung besteht zur Gruppe des 2011 verstorbenen Nobelpreisträgers für Medizin, Professor Ralph M. Steinman, dem Entdecker der dendritischen Zelle (und Ehrendoktor der Universität Innsbruck), an der Rockefeller University in New York.

Wichtige Beiträge zum Verständnis der Wirkungsweise der dendritischen Zellen stammen aus unserem Hause, wie die untenstehende Liste von ausgewählten Veröffentlichungen zeigt. Die gegenwärtige Forschung über dendritische Zellen gliedert sich in drei Bereiche:

 

Molekularbiologische und allergologische Forschung an dendritischen Zellen (Christine Heufler Tiefenthaler):
Die molekulare Grundlage für die herausragenden immunstimulierenden Eigenschaften der dendritischen Zellen ist zu großen Teilen unbekannt. Mit Hilfe moderner molekularbiologischer Methoden wurden neue, für die Funktion der dendritischen Zellen relevante Moleküle identifiziert, isoliert und charakterisiert. Diese Ansätze werden sowohl mit humanen, als auch mit murinen dendritischen Zellen durchgeführt. Mehrere interessante Moleküle sind im Rahmen dieser Projekte bereits gefunden worden (Tiefenthaler et al., 1999; Boehm, Hofer et al., 2003, Hofer et al., 2006, Ortner et al., 2011) und andere werden gerade bearbeitet. Die gegenwärtige Forschung geht in Richtung Allergologie im Humansystem. Die Interaktion von verbreiteten Allergenen der Lipocalin Gruppe mit dendritischen Zellen wird studiert. Zusammenarbeit besteht gegenwärtig u.a. mit dem Laboratory for Molecular Immunology von Prof. Michel Nussenzweig an der Rockefeller University in New York

Mitarbeiter derzeit (Jänner 2019):  a.o.Univ.Prof. Dr. Christine Heufler Tiefenthaler (Arbeitsgruppenleiterin), Susanne Neyer (BMA), MMag. Anita Geisler (technische Assistentin, dzt. karenziert), Dominik Klaver, M.Sc., PhD Student, Dr.med. Thomas Trafoier, PhD Student, Angela Romani, BMA.

 

Immunologische Forschung an dendritischen Zellen (Patrizia Stoitzner):
Im Maussystem ist das zentrale Thema die Funktion der dendritischen Zellen der Haut bei Immunantworten. Bei einem vom Österreichischen Forschungsfonds (FWF) finanzierten Projekt an Nikolaus Romani wird derzeit die Rolle des Signaltransduktionsmoleküls p14 auf die Funktion der dendritischen Zellen untersucht. In Mäusen, die speziell dieses Molekül in dendritischen Zellen deletiert haben, wird der Effekt auf die Entwicklung und Funktion dieser Immunzellen untersucht. In einem anderen vom FWF finanzierten Projekt an Patrizia Stoitzner wird die immunogene Funktion der Langerhanszellen im Kontext mit der Entstehung und der Therapie von Hautkrebs (Melanom und Platten-epithelkarzinom) untersucht. Dabei wird in verschiedenen Maustumormodellen der Phänotyp von tumor-infiltrierenden dendritischen Zellen und Effektorzellen, wie T-Zellen und natürliche Killer T-Zellen, erforscht. Weiters werden in speziellen Mausmodellen dendritische Zellen in der Haut deletiert, und die Effekte auf die Entstehung, Überwachung ("Surveillance") und Therapie von Tumoren studiert. Aus diesen Erkenntnissen werden wir neue alternative Immuntherapien entwickeln, die vorab im Maustumormodellen auf ihre Effizienz getestet werden. Mehr Details dazu in der gesonderten Website des Labors für Langerhanszellforschung. Patrizia Stoitzner ist Mitglied im FWF-finanzierten Doktoratskolleg MCBO der Medizinischen Universität und im EU Forschungskonsortium IMMUTRAIN.

Mitarbeiter derzeit (Jänner 2019): Assoz.-Prof. Dr.rer.nat. Patrizia Stoitzner (Arbeitsgruppen- und Laborleiterin), Dr.rer.nat. Christoph Tripp (PhD, Senior Scientist), Dr. Daniela Ortner-Tobider (PhD, Senior Post-Doc), Kerstin Komenda, B.Sc. (BMA), Lydia Bellmann, M.Sc. (PhD Studentin), Natasa Prokopi, M.Sc. (PhD Studentin), Athanasios (Thanasis) Seretis, M.Sc., (PhD Student), Claudia Zelle-Rieser (PhD, Senior Scientist), Univ.-Prof.i.R. Dr.rer.nat. Nikolaus Romani (Projektleiter)

Eng mit diesen Gruppen assoziiert sind die Arbeitsgruppen der Professoren Dr. Matthias Schmuth & Dr. Sandrine Dubrac, die sich in erster Linie mit der Barrierefunktion der Haut befassen, aber auch die damit zusammenhängenden Fragen der Regulation über Langerhanszellen und dermale dendritische Zellen bearbeiten.

 

Forschung mit Schwerpunkt auf der Ebene der klinischen Applikation (Patrizia Stoitzner, Nikolaus Romani):

Die Arbeiten der vergangenen Jahre haben zur Entwicklung einer inzwischen anerkannten und häufig verwendeten Methode zur Züchtung großer Mengen dendritischer Zellen aus den Monozyten des Bluts geführt (Romani et al., 1994; Romani et al., 1996). Dieser Fortschritt, zusammen mit der Identifikation von tumor-spezifischen Molekülen (Tumorantigenen), hat es erstmals realistisch gemacht, dendritische Zellen zur Immun-therapie von malignen Tumoren einzusetzen. Das Rationale hierbei ist, dendritische Zellen von Patienten ex vivo zu züchten, mit tumor-spezifischen Molekülen (Peptiden) zu "beladen" und diese so behandelten dendritischen Zellen den Patienten zu re-infundieren, in der Absicht, eine potente zytotoxische, gegen den Tumor gerichtete Immunantwort zu starten. Dieses Konzept ist in Tiermodellen vielfach bestätigt worden und weltweit laufen derzeit klinische Studien, die dieses Konzept im Wesentlichen bestätigen. Auch in Zusammenarbeit mit der Gruppe von Professor Dr. Gerold Schuler (Dermatologie, Universität Erlangen) erfolgten gemeinsame Studien, und weitere Studien sind vorgesehen. Behandelt wird auf diese Weise vorerst das maligne Melanom. Andere Tumoren werden folgen. Diese Arbeiten wurden weitgehend im Rahmen des im Juni 2015 zu Ende gegangenen FFG-finanzierten Forschungskonsortiums Oncotyrol - Center for Personalized Cancer Medicine durchgeführt; dort als gemeinsames Projekt mit Prof. Martin Thurnher vom Labor für Immunologie & Immuntherapie der Universitätsklinik für Uorologie.
In einem, zusätzlich von der Tiroler Krebshilfe gesponsorten Projekt wird die Möglichkeit untersucht, dendritische Zellen der humanen Haut durch intradermale und epikutane Applikation mit Antikörper-Antigen Konjugaten zu beladen, um dadurch die Antigenpräsentation von dendritischen Zellen zu verbessern. Dies soll zur Entwicklung von neuen Immuntherapieansätzen bei HautkrebspatientInnen führen.

Mitarbeiter derzeit (Jänner 2019):  Assoz.-Prof. Dr.rer.nat. Patrizia Stoitzner (Arbeitsgruppenleiterin), Univ.-Prof.i.R. Dr.rer.nat. Nikolaus Romani, Markus Forstner (BMA), Daniela Reider (BMA), Christina Fürhapter (M.Sc., Dipl.-MTF, Studienkoordination), Lydia Bellmann, M.Sc. (PhD Studentin), Kerstin Komenda, B.Sc. (Biomedizinische Analytikern / BMA), auf klinischer Seite a.o.Univ-Prof. Dr.med. Van Anh Nguyen und a.o.Univ.-Prof. Dr.med. Georg Weinlich.

Langerhanszellen in epidermalem Häutchenpräparat von Mäusehaut / Langerhans cells in an epidermal sheet from mouse skin (P. Stoitzner)

Langerhanszellen in epidermalem Häutchenpräparat von Mäusehaut, gefärbt mit Antikörpern gegen Langerin/CD207. Zellkerne sind mit DAPI (blau) dargestellt. / Langerhans cells in an epidermal sheet of mouse skin. Immunoperoxidase for Langerin / CD207. ©Patrizia Stoitzner.

 

Immunobiology of dendritic cells

Christine Heufler-Tiefenthaler, PhD, Associate Professor; Patrizia Stoitzner, PhD, Associate Professor, Nikolaus Romani, PhD (Professor for Experimental Dermatology emeritus), and coworkers

Laboratory for Research on Langerhans Cells ("Stoitzner lab")


Dendritic cells are leukocytes that are highly specialized for the generation of T cell-dependent immune responses. They are crucially involved in the activation of T lymphocytes, the regulation of T helper cytokine patterns, the activation and development of cytotoxic T lymphocytes, the production of antibodies, and the activation of macrophages. Dendritic cells are the only cells of the body that are able to initiate primary immune responses. Thus, they are critically positioned at the onset of any primary immune reaction. Langerhans cells have long been known to investigative dermatologists; they are the dendritic cells of the epidermis. Important data that helped to better understand the biology of dendritic cells have been corroborated in our labs as can be seen from a list of selected publications.

Dendritic cell research has a long-standing tradition at the Department of Dermatology. It has its roots in the pioneering work on Langerhans cells of Professors Klaus Wolff, Georg Stingl and Peter Fritsch. Dendritic cell research was extended and deepened under Professor Gerold Schuler. There is an active and long-lasting relationship with the laboratory of the late Professor Ralph M. Steinman, discoverer of dendritic cells and winner of the 2011 Nobel Prize for Medicine (honorary doctor of Innsbruck University, at the Rockefeller University in New York.

Three major dendritic cell-related research areas are presently covered:

Studies on the molecular biology and allergenic properties of dendritic cells (Christine Heufler-Tiefenthaler):
Much of the molecular basis for the outstanding immunostimulatory functions of dendritic cells is still unknown. By means of methods in molecular biology (e.g., differential display, microarray gene technology) novel molecules that are relevant to the function of dendritic cells are being identified, isolated and characterized. Both human and murine dendritic cells are investigated. Several interesting molecules have already been found (Tiefenthaler et al., 1999; Boehm, Hofer et al, 2003; Hofer et al 2006; Ortner et al 2011); further molecules will follow. Currently, research turns towards allergology. Interactions of common allergens and molecularly similar non-allergens from the lipocalin group with dendritic cells are studied. At present, a collaboration with Prof. Michel Nussenzweig's Laboratory of Molecular Immunology at the Rockefeller University is ongoing.

At present (January 2019) the following reseachers are part of the group: Associate Professor Christine Heufler Tiefenthaler, PhD (prinicipal investigator), Susanne Neyer (technician), MMag. Anita Geisler (technician, currently on leave), Dominik Klaver, M.Sc. (PhD student), Thomas Trafoier, MD (PhD student), Angela Romani (technician).

 

Immunological studies on dendritic cells (Patrizia Stoitzner):
In studies with mice the main topic of our research is the function of skin dendritic cells in immune responses. In a project granted to Nikolaus Romani by the Austrian Science Fund (Österreichischen Forschungsfonds (FWF), the role of the signal transduction molecule p14 in the function of dendritic cells is investigated. In mice in which this molecule is specifically deleted in dendritic cells, the effect on the development and function of immune cells is studied. In another project granted to Patrizia Stoitzner by the FWF the immunogenic function of Langerhans cells in the context of development and therapy of skin cancer (melanoma  and basal cell carcinoma) is investigated. Hereby, several different mouse tumor models are used to determine the phenotype of tumor infiltrating dendritic cells and effector cells, such as T cells and natural killer T cells. Moreover, mouse models in which skin dendritic cells can be depleted, are employed to clarify their importance for the development, surveillance and therapy of tumors. From our findings we develop novel alternative immunotherapies, which can be tested for their efficacy in mouse tumor models. More details can be found on our separate website.

At present (January 2019) the following reseachers are part of the group:  Patrizia Stoitzner, PhD (principal investigator, Associate Professor), Christoph H. Tripp, PhD (Senior Scientist), Daniela Ortner-Tobider, PhD (Senior Post-Doc, PI), Kerstin Komenda, B.Sc. (Technician), Lydia Bellmann, M.Sc. (PhD student), Natasa Prokopi, M.Sc. (PhD student), Athanasios (Thanasis) Seretis, M.Sc. (PhD student), Claudia Zelle-Rieser (PhD, senior Post-Doc), Nikolaus Romani, PhD (principal investigator, Professor emeritus).

The working group of Professor Matthias Schmuth, MD and Sandrine Dubrac, PhD is closely associated with the dendritic cell groups. While primarily dealing with the barrier function of the skin, this group also studies the role of skin dendritic cells in regulation the barrier and vice versa. The role of nuclear hormone receptors is studied in particular.

 

Research with special emphasis on the clinical application of dendritic cells for immunotherapy (Nikolaus Romani, Patrizia Stoitzner):
Research efforts of the past years have led to the development of a method to generate large numbers of dendritic cells from monocytes of the blood (Romani et al., 1994; Romani et al., 1996). This method is now widely being used. The concomitant identification of tumor-specific molecules (tumor antigens) has for the first time rendered realistic the application of dendritic cells for immunotherapy of tumors. The rationale is to use dendritic cells as a powerful adjuvant to generate anti-tumor immune responses. In principle, dendritic cells from the blood of patients are grown in vitro, "loaded" with tumor antigens (peptides), and re-infused into the patients in order to elicit a potent cytotoxic anti-tumor T cell response. This approach has proven successful in several mouse models. Many clinical trials worldwide have essentially validated the concept of dendritic cell therapy and its translation to patients. We have been collaborating with Professor Gerold Schuler (Dermatology, University of Erlangen). Malignant melanoma is the main target for these promising approaches. Most of these activities were performed within the framework of the FFG-sponsored research consortium Oncotyrol - Center for Personalized Cancer Medicine (www.oncotyrol.at) that ended in June 2015. There, our Dermatology group has joined forces with the group of Prof. Martin Thurnher from the Laboratory of Immunology & Immunotherapy at the Urology Department of the Medical University of Innsbruck.
In a project, additionally sponsored by the Tyrolean Cancer Society (Tiroler Krebshilfe) we are investigating the possiblity to target dendritic cells in the skin with antibody-antigen conjugates by intradermal and epicutaneous application. This should lead to improved antigen presentation by dendritic cells and, as a consequence, to more efficient T cell responses against cancer. This has the potential to greatly enhance and amplify immunotherapies using immune checkpoint inhibitors for skin cancer patients.

At present (January 2019) the following reseachers are part of the group:  Patrizia Stoitzner, PhD, Associate Professor (principal investigator), Markus Forstner (technician), Daniela Reider (technician), Christina Fürhapter (M.Sc., study coordinator), Lydia Bellmann, M.Sc. (PhD student), Kerstin Komenda, B.Sc. (Technician), Nikolaus Romani, PhD, Professor em. (principal investigator), and as clinical partners Van Anh Nguyen, MD, Associate Professor, and Georg Weinlich, MD, Associate Professor.

 

Langerhanszellen in epidermalem Häutchenpräparat von Mäusehaut, immunfluoreszenzmethodisch gefärbt mit Antikörpern gegen Langerin/CD207 /rot) und MHC II (grün). Zellkerne sind mit DAP (blau) dargestellt. / Langerhans cells in an epidermal sheet of mouse skin. Immunfluorescence for Langerin / CD207 (red) and MHC II (green). Nuclei are stained with DAPI (blue). ©Bernhard Haid, 2006

 

Ausgewählte Veröffentlichungen über Forschungen an dendritischen Zellen (Stand Jänner 2019)   --   Selected dendritic cell-relevant publications (as of January 2019)

Sparber F, Dolowschiak T, Mertens S, Lauener L, Clausen BE, Joller N, Stoitzner P, Tussiwand R, LeibundGut-Landmann S. Langerin+ DCs regulate innate IL-17 production in the oral mucosa during Candida albicans-mediated infection. PLoS Pathog. 14(5):e1007069. May 2018. free article

Lutz M, Strobl H, Schuler G, Romani N. GM-CSF monocyte-derived cells and Langerhans cells as part of the dendritic cell family. Frontiers in Immunology, 8:1388, 2017. free article

Ortner D, Tripp CH, Komenda K, Dubrac S, Zelger B, Hermann M, Doppler D,  Tymoszuk PZ, Boon L, Clausen BE, Stoitzner P. Langerhans cells and NK cells cooperate in the inhibition of chemical skin carcinogenesis. Oncoimmunology, 6(2):e1260215, 2016. free article

Buschow SI, Ramazzotti M, Reinieren-Beeren IMJ, Heinzerling LM, Westdorp H, Stefanini I, Beltrame L, Hato SV, Ellebæk E, Gross S, Nguyen VA, Weinlich G, Ragoussis J, Baban D, Schuler-Thurner B, Svane IM, Romani N, Austyn JM, De Vries IJM, Schuler G, Cavalieri D, Figdor CG. Survival of metastatic melanoma patients after dendritic cell vaccination correlates with expression of leukocyte phosphatidylethanolamine-binding protein 1 / Raf Kinase inhibitory protein. Oncotarget. 8:67439-67456, 2017. free article

Lutz MB, Inaba K, Schuler G, Romani N. Still Alive and Kicking: In-Vitro-Generated GM-CSF Dendritic Cells! Immunity. 44:1-2, 2016. free article

Clausen BE, Stoitzner P. Functional specialization of skin dendritic cell subsets in regulating T cell responses. Front Immunol, 6:534, 2015. free article

Mairhofer DG, Ortner D, Tripp CH, Schaffenrath S, Fleming V, Heger L, Komenda K, Reider D, Dudziak D, Chen S, Becker JC, Flacher V, Stoitzner P. Impaired gp100-specific CD8+ T cell responses in the presence of myeloid-derived suppressor cells in a spontaneous mouse melanoma model. J Invest Dermatol, 135:2785-2793, 2015. free article

Haid B, Schlögl D, Hermann M, Tripp CH, Stoitzner P, Romani N, Flacher V. Langerhans cells in the sebaceous glands of the murine skin. Exp Dermatol. 2015 Jul 14. doi: 10.1111/exd.12803. [Epub ahead of print] free article

Posch B, Irsara C, Gamper FS, Hermann M, Bindreither D, Fuchs D, Reider N, Redl B, Heufler C. Allergenic Can f 1 and its human homologue Lcn-1 direct dendritic cells to induce divergent immune responses. J Cell Mol Med, 19:2375-2384, 2015. free article

Romani N, Young JW. Langerhans cells: straight from blood to skin? Blood, 125:420-422, 2015 (Commentary "Inside Blood")
 
Sparber F, Tripp CH, Komenda K, Scheffler JM, Clausen BE, Huber LA, Romani N, Stoitzner P. The late endosomal adaptor molecule p14 (LAMTOR2) regulates TGFβ1-mediated homeostasis of Langerhans cells. J Invest Dermatol, 135:119-129, 2015. free PMC article
 
Stoitzner P, Schaffenrath S, Tripp CH, Reider D, Komenda K, Del Frari B, Djedovic G, Ebner S, Romani N. Human skin dendritic cells can be targeted in situ by intradermal injection of antibodies against lectin receptors. Exp Dermatol, 23:909-915, 2014. free article
 
Flacher V, Tripp CH, Mairhofer D, Steinman RM, Stoitzner P, Idoyaga J, Romani N. Antigen capture via CD207 molecules on skin dendritic cells can either prime or tolerize CD8+T cells. EMBO Mol Med, 6:1191-1204, 2014 free article
 
Sparber F. Langerhans cells - an update. J Dtsch Dermatol Ges,12:1107-1111, 2014
 
Scheffler JM, Sparber F, Herrmann C, Blitz J, Romani N, Stoitzner P, Huber LA. LAMTOR2 regulates dendritic cell homeostasis through FLT3 dependent mTOR signaling. Nature Communications, 5:5138, 2014 free article
 
Sparber F, Scheffler JM, Amberg N, Tripp CH, Heib V, Hermann M, Zahner SP, Clausen BE, Reizis B, Huber LA, Stoitzner P, Romani N. The late endosomal adaptor molecule p14 (LAMTOR2) represents a novel regulator of Langerhans cell homeostasis. Blood, 123:217-227, 2014  free article and commentary
 
Grabher D, Hofer S, Ortner D, Heufler C. In human monocyte derived dendritic cells SOCS1 interacting with CYTIP induces the degradation of CYTIP by the proteasome. PLOS ONE, 8: e57538. doi:10.1371/journal.pone.0057538 free article
 
Romani N, Tripp CH, Stoitzner P. Langerhans cells come in waves. Commentary. Immunity, 37:766-768, 2012. Free article
 
Flacher V, Tripp CH, Haid B, Kissenpfennig A, Malissen B, Stoitzner P, Idoyaga J, Romani N. Skin langerin+ dendritic cells transport intradermally injected anti-DEC-205 antibodies but are not essential for subsequent cytotoxic CD8+ T cell responses. J Immunol, 188:2146-2155, 2012
 
Heib V, Sparber F, Tripp CH, Ortner D, Stoitzner P, Heufler C. Cytip regulates dendritic-cell function in contact hypersensitivity. CYTIP is an important regulator of immer responses in vivo. Eur J Immunol, 42:589-597, 2012 free article
 
Romani N, Flacher V, Tripp CH, Sparber F, Ebner S, Stoitzner P. Targeting skin dendritic cells to improve intradermal vaccination. Current Topics in Microbiology & Immunology, 351:113-138, 2012 (Review Article)
 
Schwingshackl P, Obermoser G, Nguyen VA, Fritsch P, Sepp N, Romani N. Distribution and Maturation of Skin Dendritic Cell Subsets in Two Forms of Cutaneous T Cell Lymphoma - Mycosis Fungoides and Sézary Syndrome. Acta Derm Venereol, 92:269-275, 2012  free article
 
Ortner D, Grabher D, Hermann M, Kremmer E, Hofer S, Heufler H. The Adaptor Protein Bam32 in Human Dendritic Cells Participates in the Regulation of MHC Class I-Induced CD8+ T Cell Activation. J Immunol, 187:3972-3978, 2011 free article
 
Dubrac S, Elentner A, Schoonjans K, Auwerx J, Schmuth M., Lack of IL-2 in PPAR-alpha deficient mice triggers allergic contact dermatitis by affecting regulatory T cells. Eur J Immunol, 41:1980-1991, 2011
 
Nguyen VA, Dubrac S, Huter O, Del Frari B, Romani N, Ebner S. CD34+ derived Langerhans cell-like cells are different from epidermal Langerhans cells in their response to thymic stromal lymphopoietin. J Cell Mol Med, 15:1847-1856, 2011
 
Sparber F, Tripp CH, Hermann M, Romani N, Stoitzner P. Langerhans cells and dermal dendritic cells capture protein antigens in the skin: possible targets for vaccination through skin. Immunobiology, 215:770-779, 2010 free article
 
Stoitzner P, Sparber F, Tripp CH. Langerhans cells as targets for immunotherapy against skin cancer. Immunol Cell Biol, 88:431-437, 2010 (Review Article) free article
 
Dubrac S, Schmuth M, Ebner S. Atopic Dermatitis: The role of Langerhans cells in disease pathogenesis. Immunol Cell Biol, 88:400-409, 2010 (Review Article)
 
Romani N, Thurnher M, Idoyaga J, Steinman RM, Flacher V. Targeting of antigens to skin dendritic cells: possibilities to enhance vaccine efficacy. Immunol Cell Biol, 88:424-430, 2010 (Review Article) free article
 
Romani N, Clausen BE, Stoitzner P. Langerhans Cells & More: Langerin-expressing dendritic cell subsets in the skin. Immunol Rev, 234:121-143, 2010 (Review Article) free article
 
Stoitzner P, Stingl G, Merad  M, Romani N. Langerhans Cells at the Interface of Medicine, Science and Industry. J Invest Dermatol, 130: 331-335, 2010 (Meeting Report)
 
Tripp CH, Ebner S, Ratzinger G, Romani N, Stoitzner P. Conditioning of the injection site with CpG enhances the migration of adoptively transferred dendritic cells and endogenous CD8+ T cell responses. J Immunother, 33:115-125, 2010
 
Flacher V, Tripp CH, Stoitzner P, Haid B, Ebner S, Del Frari B, Koch F, Park CG, Steinman RM, Idoyaga J, Romani N. Epidermal Langerhans cells rapidly capture and present antigens from C-type lectin-targeting antibodies deposited in the dermis. J Invest Dermatol, 130:755-762, 2010 free article
 
Tripp CH, Sparber F, Hermans IF, Romani N, Stoitzner P. Glycolipids injected into the skin are presented to NKT cells in the draining lymph node independent of skin dendritic cells. J Immunol, 182:7644-7654, 2009 free article
 
Elentner A, Finke D, Schmuth M, Chappaz S, Ebner S, Malissen B, Kissenpfennig A, Romani N, Dubrac S. Langerhans cells are critical in the development of atopic dermatitis-like inflammation and symptoms in mice. J Cell Mol Med, 13:2658-2672, 2009
 
Flacher V, Sparber F, Tripp CH, Romani N, Stoitzner P. Targeting of epidermal Langerhans cells with antigenic proteins  -  attempts to harness their properties for immunotherapy. Cancer Immunol Immunother, 58:1137-1147, 2009
 
Stoitzner P, Green LK, Jung JY, Price KM, Tripp CH, Malissen B, Kissenpfennig A, Hermans I, Ronchese F. Tumor immunotherapy by epicutaneous immunization requires Langerhans cells. J Immunol, 180:1991-1998, 2008
 
Ebner S, Nguyen VA, Forstner M, Wang Y-H, Wolfram DM, Fritsch P, Liu Y-J, Romani N. Thymic stromal lymphopoietin converts human epidermal Langerhans cells antigen presenting cells that induce pro-allergic T cells. J Allergy Clin Immunol, 119:982-990, 2007
 
Dubrac S, Stoitzner P, Pirkebner D, Elentner A, Schoonjans K, Auwerx J, Saeland S, Hengster P, Fritsch P, Romani N, Schmuth M. PPAR-alpha activation inhibits Langerhans cell function. J Immunol, 178:4362-4372, 2007
 
Stoitzner P, Tripp CH, Eberhart A, Price KM, Jung JY, Bursch L, Ronchese F, Romani N. Langerhans cells cross-present antigen derived from skin. Proc Natl Acad Sci USA, 103:7783-7788, 2006 free article
 
Hofer S, Pfeil K, Niederegger H, Ebner S, Nguyen VA, Kremmer E, Auffinger M, Neyer S, Fürhapter C, Heufler C. Dendritic cells regulate T cell de-attachment through the integrin-interacting protein CYTIP. Blood, 107:1003-1009, 2006 free article
 
Romani N, Tripp CH, Ratzinger G, Heufler C, Koch F, Saeland S, Stoitzner P. Epidermal Langerhans Cells. In Dendritic Cells , ed. Steinkasserer A, Romani N, Lutz MB. Wiley-VCH, pp.73-100, 2006
 
Kissenpfennig A, Henri S, Dubois B, Laplace-Builhé C, Perrin P, Romani N, Tripp CH, Douillard P, Leserman L, Kaiserlian D, Saeland S, Davoust J, Malissen B. Dynamics and function of Langerhans cells in vivo: Dermal dendritic cells colonize lymph node areas distinct from slower migrating Langerhans cells. Immunity, 22:643-654, 2005
 
Ebner S, Ehammer Z, Holzmann S, Schwingshackl P, Forstner M, Stoitzner P, Huemer GM, Fritsch P, Romani N. Expression of C-type lectin receptors by subsets of dendritic cells in human skin. Int Immunol, 16: 877-887, 2004 free article
 
Holzmann S, Tripp CH, Schmuth M, Janke K, Koch F, Saeland S, Stoitzner P, Romani N. A model system using tape stripping for characterization of Langerhans cell-precursors in vivo. J Invest Dermatol, 122:1165-1174, 2004 free article
 
Tripp CH, Chang-Rodriguez S, Stoitzner P, Holzmann S, Stössel H, Douillard P, Saeland S, Koch F, Elbe-Bürger A, Romani N. Ontogeny of Langerin / CD207 expression in the epidermis of mice. J Invest Dermatol, 122:670-672, 2004 free article
 
Boehm T, Hofer S, Winklehner P, Kellersch B, Geiger C, Trockenbacher A, Neyer S, Fiegl H, Ebner S, Ivarsson L, Schneider R, Kremmer E, Heufler C, Kolanus W. Attenuation of cell adhesion in lymphocytes is regulated by CYTIP, a protein which mediates signal complex sequestration. EMBO J. 22:1014-1024, 2003
 
Stoitzner P, Holzmann S, McLellan AD, Ivarsson L, Stössel H, Kapp M, Kämmerer U, Douillard P, Kämpgen E, Koch F, Saeland S Romani N. 2003. Visualization and characterization of migratory Langerhans cells in murine skin and lymph nodes by antibodies against Langerin / CD207. J Invest Dermatol, 120:266-274, 2003 free article
 
Hofer S, Ivarsson L, Stoitzner P, Auffinger M, Rainer C, Romani N, Heufler C. 2003. Adenosine slows migration of dendritic cells but does not affect other aspects of dendritic cell maturation. J Invest Dermatol, 121:300-307, 2003
 
Schuler-Thurner B, Schultz ES, Berger TG, Weinlich G, Ebner S, Woerl P, Bender A, Feuerstein B, Fritsch PO, Romani N, Schuler G. Rapid induction of tumor-specific type 1 T helper cells in metastatic melanoma patients by vaccination with mature, cryopreserved, peptide-loaded monocyte-derived dendritic cells. J Exp Med, 195:1279-1288, 2002
 
Ebner S, Hofer S, Nguyen VA, Fürhapter C, Herold M, Fritsch P, Heufler C, Romani N. A novel role for IL-3: Human monocytes cultured in the presence of IL-3 + IL-4 differentiate into dendritic cells that produce less IL-12 and shift helper T cell responses towards a TH2 cytokine pattern. J Immunol, 168:6199-6207, 2002
 
Frank I, Piatak M Jr, Stössel H, Romani N, Bonnyay D, Lifson JD, Pope M. Infectious and whole inactivated simian immunodeficiency viruses interact similarly with primate dendritic cells (DCs): Differential intracellular fate of virions in mature and immature DCs. J Virol, 76:2936-2951, 2002
 
Ratzinger G, Stoitzner P, Ebner S, Lutz MB, Layton GT, Rainer C, Senior RM, Shipley MJ, Fritsch P, Schuler G, Romani N. Matrix metalloproteinases 9 and 2 are necessary for the migration of Langerhans cells and dermal dendritic cells from human and murine skin. J Immunol, 168:4361-4371, 2002
 
Stoitzner P, Pfaller K, Stössel H, Romani NA close-up view of migrating Langerhans cells in the skin. J Invest Dermatol, 118:117-125, 2002
 
Reider N, Reider D, Ebner S, Holzmann S, Herold M, Fritsch P, Romani N. Dendritic cells contribute to the development of atopy by an insufficiency in IL-2 production. J Allergy Clin Immunol, 109:89-95, 2002
 
Valladeau J, Clair-Moninot V, Dezutter-Dambuyant C, Pin J-J, Kissenpfennig A, Mattéi M-G, Ait-Yahia S, Bates EEM, Malissen B, Koch F, Fossiez F, Romani N, Lebecque S, Saeland S. Identification of mouse Langerin / CD207 in Langerhans cells and some dendritic cells of lymphoid tissues. J Immunol, 168:782-792, 2002
 
Ebner S, Ratzinger G, Krösbacher B, Schmuth M, Weiss A, Reider D, Kroczek RA, Herold M, Heufler C, Fritsch P, Romani N. Production of Interleukin-12 by human monocyte-derived dendritic cells is optimal when the stimulus is given at the onset of maturation, and is further enhanced by interleukin-4. J Immunol, 166:633-641, 2001
 
Stoitzner P, Ratzinger G, Koch F, Janke K, Kaser A, Tilg H, Schoeller T, Cruikshank WW, Fritsch P, Romani N. Interleukin-16 supports the migration of Langerhans cells, partly in a CD4-independent way. J Invest Dermatol, 116: 641-649, 2001
 
Ebner S, Neyer S, Hofer S, Nussbaumer W, Romani N, Heufler C. Generation of large numbers of dendritic cells from leukocyte removal filters for whole blood - an alternative to standard buffy coats. J Immunol Methods, 252:93-104, 2001
 
Tiefenthaler M, Marksteiner R, Neyer S, Koch F, Hofer S, Schuler G, Nussenzweig M, Schneider R, Heufler C. M1204, a novel 2'5' oligoadenylate synthetase with a ubiquitin-like extension is induced during maturation of murine dendritic cells. J Immunol, 163:760-5, 1999
 
Stoitzner P, Zanella M, Ortner U, Lukas M, Tagwerker A, Janke K, Lutz MB, Schuler G, Echtenacher B, Ryffel B, Koch F, Romani N. Migration of Langerhans cells and dermal dendritic cells in murine skin organ cultures: Augmentation by TNF-a and Interleukin-1ß. J Leukocyte Biol, 66:462-470, 1999
 
Ebner S, Lenz A, Reider D, Fritsch P, Schuler G, Romani N. Expression of maturation- / migration-related molecules on human dendritic cells from blood and skin. Immunobiology, 198:568-587, 1998
 
Weinlich G, Heine M, Stössel H, Zanella M, Stoitzner P, Ortner U, Smolle J, Koch F, Sepp NT, Schuler G, Romani N.. Entry into afferent lymphatics and maturation in situ of migrating cutaneous dendritic cells. J Invest Dermatol, 110:441-448, 1998
 
Welte T, Koch F, Schuler G, Lechner J, Doppler W, Heufler C. Granulocyte-macrophage colony-stimulating factor induces a unique set of STAT factors in murine dendritic cells. Eur J Immunol, 27:2737-2740, 1997
 
Romani N, Reider D, Heuer M, Ebner S, Eibl B, Niederwieser D, Schuler G. Generation of mature dendritic cells from human blood: An improved method with special regard to clinical applicability. J Immunol Methods, 196:137-151, 1996
 
Koch F, Stanzl U, Jennewein P, Janke K, Heufler C, Kämpgen E, Romani N, Schuler G. High level Interleukin-12 production by murine dendritic cells: upregulation via MHC class II and CD40 molecules and downregulation by Interleukin-4 and Interleukin-10. J Exp Med, 184:741-746, 1996
 
Heufler C, Koch F, Stanzl U, Topar G, Wysocka M, Trinchieri G, Enk A, Steinman RM, Romani N, Schuler G. Interleukin-12 is produced by dendritic cells and mediates TH1 development as well as Interferon-gamma production by TH1 cells. Eur J Immunol, 26:659-668, 1996
 
Lukas M, Stössel H, Hefel L, Imamura S, Fritsch P, Sepp NT, Schuler G, Romani N. Human cutaneous dendritic cells migrate through dermal lymphatic vessels in a skin organ culture model. J Invest Dermatol, 106:1293-1299, 1996
 
Ortner U, Inaba K, Koch F, Heine M, Miwa M, Schuler G, Romani N. An improved method to obtain murine migratory cutaneous dendritic cells. J Immunol Methods, 193:71-79, 1996
 
Jiang W, Swiggard WJ, Heufler C, Peng M, Mirza A, Steinman RM, Nussenzweig MC. The receptor DEC-205 expressed by dendritic cells and thymic epithelial cells is involved in antigen processing. Nature, 375:151-155, 1995
 
Koch F, Trockenbacher B, Kämpgen E, Grauer O, Stössel H, Livingstone AM, Schuler G, Romani N. Antigen processing in populations of mature murine dendritic cells is caused by subsets of incompletely matured cells. J Immunol, 155:93-100, 1995
 
Romani N, Gruner S, Brang D, Kämpgen E, Lenz A, Trockenbacher B, Konwalinka G, Fritsch P, Steinman RM, Schuler G. Proliferating dendritic cell progenitors in human blood. J Exp Med, 180:83-93, 1994
 
Kämpgen E, Koch F, Heufler C, Eggert A, Gill LL, Gillis S, Dower SK, Romani N, Schuler G. Understanding the dendritic cell lineage through a study of cytokine receptors. J Exp Med, 179:1767, 1994
 
Pope M, Betjes MGH, Romani N, Hirmand H, Cameron PU, Hoffman L, Gezelter S, Schuler G, Steinman RM. Conjugates of dendritic cells and memory T lymphocytes from skin facilitate productive infection with human immunodeficiency virus-1. Cell, 78:389-398, 1994
 
Heufler C, Topar G, Grassegger A, Stanzl U, Koch F, Romani N, Namen AE, Schuler G. Interleukin-7 is produced by murine and human keratinocytes. J Exp Med, 178:1109-1114, 1993
 
Lenz A, Heine M, Schuler G, Romani N. Human and murine dermis contain dendritic cells: Isolation by means of a novel method and phenotypical and functional characterization. J Clin Invest, 92:2587-2596, 1993 free article
 
Heufler C, Topar G, Koch F, Trockenbacher B, Kämpgen E, Romani N, Schuler G. Cytokine gene expression in murine epidermal cell suspensions. Interleukin-1ß and Macrophage Inflammatory Protein-1-alpha are selectively expressed in Langerhans cells but are differentially regulated in culture. J Exp Med, 176:1221-1226 , 1992
 
Koch F, Kämpgen E, Schuler G, Romani N. Effective enrichment of murine epidermal Langerhans cells by a modified - "mismatched" - panning technique. J Invest Dermatol, 99:803-807, 1992
 
Agger R, Witmer-Pack M, Romani N, Stössel H, Swiggard WJ, Metlay JP, Storozynsky E, Freimuth P, Steinman RM. Two populations of splenic dendritic cells detected with M342, a new monoclonal to an intracellular antigen of interdigitating dendritic cells and some B lymphocytes. J Leukocyte Biol, 52:34-42, 1992
 
Kämpgen E, Koch N, Koch F, Stöger P, Heufler C, Schuler G, Romani N. Class II major histocompatibility complex molecules of murine dendritic cells: Synthesis, sialylation of invariant chain, and antigen processing capacity are down-regulated upon culture. Proc Natl Acad Sci USA 88:3014-3018, 1991
 
Koch F, Heufler C, Kämpgen E, Schneeweiss D, Böck G, Schuler G. Tumor necrosis factor alpha maintains the viability of murine epidermal Langerhans cells in culture but in contrast to granulocyte/macrophage colony-stimulating factor without inducing their functional maturation. J Exp Med, 171:159-171, 1990
 
Stössel H, Koch F, Kämpgen E, Stöger P, Lenz A, Heufler C, Romani N, Schuler G. Disappearance of certain acidic organelles [endosomes and Langerhans cell granules] accompanies loss of antigen processing capacity upon culture of epidermal Langerhans cells. J Exp Med, 172:1471-1482, 1990.
 
Romani N, Lenz A, Glassel H, Stössel H, Stanzl U, Majdic O, Fritsch P, Schuler G. Cultured human Langerhans cells resemble lymphoid dendritic cells in phenotype and function. J Invest Dermatol, 93:600-609, 1989.
 
Romani N, Koide S, Crowley M, Witmer-Pack M, Livingstone AM, Fathman CG, Inaba K, Steinman RM. Presentation of exogenous protein antigens by dendritic cells to T cell clones: intact protein is presented best by immature epidermal Langerhans cells. J Exp Med, 169:1169-1178, 1989.
 
Heufler C, Koch F, Schuler G. Granulocyte-macrophage colony-stimulating factor and interleukin-1 mediate the maturation of murine epidermal Langerhans cells into potent immunostimulatory dendritic cells. J Exp Med, 167:700-705, 1988.
 
Romani N, Schuler G, Fritsch PO. The ontogeny of Ia-positive and Thy-1 positive leukocytes of murine epidermis. J Invest Dermatol, 86:129-133, 1986.
 
Schuler, G. and R. M. Steinman. Murine epidermal Langerhans cells mature into potent immunostimulatory dendritic cells in vitro. J Exp Med, 161:526-546, 1985.
 
Romani N, Stingl G, Tschachler E, Witmer MD, Steinman RM, Shevach EM, Schuler G. The Thy-1 bearing cell of murine epidermis. A distinctive leukocyte perhaps related to natural killer cells. J Exp Med, 161:1368-1383, 1985.

 

 

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