Premium
Steady state migratory RelB + langerin + dermal dendritic cells mediate peripheral induction of antigen‐specific CD4 + CD25 + Foxp3 + regulatory T cells
Author(s) -
Azukizawa Hiroaki,
Döhler Anja,
Kanazawa Nobuo,
Nayak Arnab,
Lipp Martin,
Malissen Bernard,
Autenrieth Ingo,
Katayama Ichiro,
Riemann Marc,
Weih Falk,
BerberichSiebelt Friederike,
Lutz Manfred B.
Publication year - 2011
Publication title -
european journal of immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.272
H-Index - 201
eISSN - 1521-4141
pISSN - 0014-2980
DOI - 10.1002/eji.201040930
Subject(s) - foxp3 , biology , il 2 receptor , langerin , antigen , peripheral tolerance , immunology , relb , cd40 , t cell , immune tolerance , antigen presenting cell , microbiology and biotechnology , immune system , dendritic cell , cytotoxic t cell , transcription factor , in vitro , nfkb1 , biochemistry , gene
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.