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Steady state migratory RelB(+) Langerin(+) dermal dendritic cells mediate peripheral induction of antigen-specific CD4(+) CD25(+) Foxp3(+) regulatory T cells

Item Type:Article
Title:Steady state migratory RelB(+) Langerin(+) dermal dendritic cells mediate peripheral induction of antigen-specific CD4(+) CD25(+) Foxp3(+) regulatory T cells
Creators Name:Azukizawa, H. and Doehler, A. and Kanazawa, N. and Nayak, A. and Lipp, M. and Malissen, B. and Autenrieth, I. and Katayama, I. and Riemann, M. and Weih, F. and Berberich-Siebelt, F. and Lutz, M.B.
Abstract:Tolerance to self-antigens expressed in peripheral organs is maintained by CD4(+) CD25(+) Foxp3(+) regulatory T cells (Treg), which are generated as a result of thymic selection or peripheral induction. Here, we demonstrate that steady state migratory dendritic cells (DC) from the skin mediated Treg conversion in draining lymph nodes of mice. These DC 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 DC. These DC transported and directly presented soluble OVA provided by subcutaneously 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 (LC), mediated conversion of naive OT-II×RAG-1(-/-) T cells into proliferating CD4(+) CD25(+) Foxp3(+) Treg. Thus, our data suggest that steady state migratory RelB(+) TGF-β(+) Langerin(+) dermal DC mediate peripheral Treg conversion for epidermal antigen in skin-draining lymph nodes.
Keywords:Cell Trafficking, Dendritic Cells, Immune Regulation, Regulatory T Cells, Tolerance, Animals, Mice
Source:European Journal of Immunology
ISSN:0014-2980
Publisher:Wiley (U.S.A.)
Volume:41
Number:5
Page Range:1420-1434
Date:May 2011
Official Publication:https://doi.org/10.1002/eji.201040930
PubMed:View item in PubMed

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