1. Steady state migratory RelB+ langerin+ dermal dendritic cells mediate peripheral induction of antigen-specific CD4+ CD25+ Foxp3+ regulatory T cells
- Author
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Arnab Nayak, Hiroaki Azukizawa, Ingo B. Autenrieth, Falk Weih, Anja Döhler, Ichiro Katayama, Marc Riemann, Bernard Malissen, Friederike Berberich-Siebelt, Manfred B. Lutz, Martin Lipp, Nobuo Kanazawa, Osaka University, Course of integrated medicine, Department of Dermatology, Lehrstuhl für Regelungstechnik [Erlangen], Friedrich-Alexander Universität Erlangen-Nürnberg (FAU), Julius-Maximilians-Universität Würzburg [Wurtzbourg, Allemagne] (JMU), Max Delbrück Center for Molecular Medicine [Berlin] (MDC), Helmholtz-Gemeinschaft = Helmholtz Association, Centre d'Immunologie de Marseille - Luminy (CIML), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Wilhelm-Schickard-Institut für Informatik · Lehrstuhl GRaphisch-Interaktive Systeme (WSI/GRIS), Eberhard Karls Universität Tübingen = Eberhard Karls University of Tuebingen, Leibniz Institute on Aging - Fritz Lipmann Institute (FLI), Leibniz Association, Julius-Maximilians-Universität Würzburg (JMU), and Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Aix Marseille Université (AMU)
- Subjects
MESH: Interleukin-2 Receptor alpha Subunit ,MESH: Antigens, CD4 ,MESH: NF-kappa B ,Fluorescent Antibody Technique ,MESH: Lymph Nodes ,MESH: Transcription Factor RelB ,MESH: Receptors, CCR7 ,T-Lymphocytes, Regulatory ,Major Histocompatibility Complex ,Mice ,0302 clinical medicine ,Cell Movement ,Transforming Growth Factor beta ,MESH: Microscopy, Confocal ,Immunology and Allergy ,MESH: Animals ,IL-2 receptor ,MESH: Antigens, CD ,MESH: Cell Movement ,MESH: Fluorescent Antibody Technique ,Skin ,MESH: Langerhans Cells ,0303 health sciences ,Microscopy, Confocal ,integumentary system ,biology ,RELB ,NF-kappa B ,FOXP3 ,hemic and immune systems ,Cell Differentiation ,Forkhead Transcription Factors ,Cell biology ,Self Tolerance ,MESH: Self Tolerance ,Antigens, Surface ,CD4 Antigens ,[SDV.IMM]Life Sciences [q-bio]/Immunology ,Integrin alpha Chains ,MESH: Cell Differentiation ,Receptors, CCR7 ,MESH: Immunophenotyping ,Langerin ,MESH: Mice, Transgenic ,MESH: Antigens, Surface ,Immunology ,chemical and pharmacologic phenomena ,Mice, Transgenic ,Major histocompatibility complex ,Immunophenotyping ,03 medical and health sciences ,MESH: Major Histocompatibility Complex ,MESH: Skin ,Antigen ,MESH: Mice, Inbred C57BL ,MESH: Forkhead Transcription Factors ,Antigens, CD ,MESH: Mannose-Binding Lectins ,Animals ,Lectins, C-Type ,MESH: Mice ,MESH: Transforming Growth Factor beta ,030304 developmental biology ,CD86 ,CD40 ,MESH: T-Lymphocytes, Regulatory ,Transcription Factor RelB ,MESH: Integrin alpha Chains ,Interleukin-2 Receptor alpha Subunit ,Mice, Inbred C57BL ,Mannose-Binding Lectins ,Langerhans Cells ,biology.protein ,Lymph Nodes ,MESH: Lectins, C-Type ,030215 immunology - Abstract
International audience; Tolerance to self-antigens expressed in peripheral organs is maintained by CD4(+) CD25(+) Foxp3(+) Treg cells, which are generated as a result of thymic selection or peripheral induction. Here, we demonstrate that steady-state migratory DCs from the skin mediated Treg conversion in draining lymph nodes of mice. These DCs displayed a partially mature MHC II(int) CD86(int) CD40(hi) CCR7(+) phenotype, used endogenous TGF-β for conversion and showed nuclear RelB translocation. Deficiency of the alternative NF-κB signaling pathway (RelB/p52) reduced steady-state migration of DCs. These DCs transported and directly presented soluble OVA provided by s.c. implanted osmotic minipumps, as well as cell-associated epidermal OVA in transgenic K5-mOVA mice to CD4(+) OVA-specific TCR-transgenic OT-II T cells. The langerin(+) dermal DC subset, but not epidermal Langerhans cells, mediated conversion of naive OT-II×RAG-1(-/-) T cells into proliferating CD4(+) CD25(+) Foxp3(+) Tregs. Thus, our data suggest that steady-state migratory RelB(+) TGF-β(+) langerin(+) dermal DCs mediate peripheral Treg conversion in response to epidermal antigen in skin-draining lymph nodes.
- Published
- 2010