title: Steady state migratory RelB+ langerin+ dermal dendritic cells mediate peripheral induction of antigen-specific CD4+ CD25+ Foxp3+ regulatory T cells.
abstract: 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.
authors.affiliation: Department of Dermatology, University Hospital Erlangen, Erlangen, Germany.
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Azukizawa
authors.forename: Anja
authors.initials: A
authors.lastname: Döhler
authors.forename: Nobuo
authors.initials: N
authors.lastname: Kanazawa
authors.forename: Arnab
authors.initials: A
authors.lastname: Nayak
authors.forename: Martin
authors.initials: M
authors.lastname: Lipp
authors.forename: Bernard
authors.initials: B
authors.lastname: Malissen
authors.forename: Ingo
authors.initials: I
authors.lastname: Autenrieth
authors.forename: Ichiro
authors.initials: I
authors.lastname: Katayama
authors.forename: Marc
authors.initials: M
authors.lastname: Riemann
authors.forename: Falk
authors.initials: F
authors.lastname: Weih
authors.forename: Friederike
authors.initials: F
authors.lastname: Berberich-Siebelt
authors.forename: Manfred B
authors.initials: MB
authors.lastname: Lutz
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000032:analysis; D000954:Antigens, Surface / Q000032:analysis; D015704:CD4 Antigens / Q000032:analysis; D002454:Cell Differentiation; D002465:Cell Movement; D005455:Fluorescent Antibody Technique; D051858:Forkhead Transcription Factors / Q000235:genetics / Q000378:metabolism; D016130:Immunophenotyping; D039001:Integrin alpha Chains / Q000032:analysis; D053645:Interleukin-2 Receptor alpha Subunit / Q000032:analysis; D007801:Langerhans Cells / Q000276:immunology* / Q000378:metabolism; D037181:Lectins, C-Type / Q000032:analysis; D008198:Lymph Nodes / Q000276:immunology* / Q000378:metabolism; D008285:Major Histocompatibility Complex; D037241:Mannose-Binding Lectins / Q000032:analysis; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D018613:Microscopy, Confocal; D016328:NF-kappa B / Q000172:deficiency / Q000276:immunology; D054400:Receptors, CCR7 / Q000032:analysis; D017634:Self Tolerance; D012867:Skin / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000378:metabolism; D051841:Transcription Factor RelB / Q000032:analysis; D016212:Transforming Growth Factor beta / Q000378:metabolism
chemical_list: D015703:Antigens, CD; D000954:Antigens, Surface; D015704:CD4 Antigens; C515371:Ccr7 protein, mouse; C498497:Cd207 protein, mouse; D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; D039001:Integrin alpha Chains; D053645:Interleukin-2 Receptor alpha Subunit; D037181:Lectins, C-Type; D037241:Mannose-Binding Lectins; D016328:NF-kappa B; D054400:Receptors, CCR7; C497594:Relb protein, mouse; D016212:Transforming Growth Factor beta; C091367:alpha E integrins; D051841:Transcription Factor RelB