Steady state migratory RelB+ langerin+ dermal dendritic cells mediate peripheral induction of antigen‐specific CD4+CD25+Foxp3+ regulatory T cells

• Published in: European journal of immunology 2011-05, Vol.41 (5), p.1420-1434
• Main Authors: Azukizawa, Hiroaki, Döhler, Anja, Kanazawa, Nobuo, Nayak, Arnab, Lipp, Martin, Malissen, Bernard, Autenrieth, Ingo, Katayama, Ichiro, Riemann, Marc, Weih, Falk, Berberich‐Siebelt, Friederike, Lutz, Manfred B.
• Format: Article
• Language: English
• Subjects: Animals; Antigens, CD; Antigens, CD - analysis; Antigens, CD4; Antigens, Surface; Antigens, Surface - analysis; CD4 Antigens - analysis; Cell Differentiation; Cell Movement; Cell trafficking; DCs; Fluorescent Antibody Technique; Forkhead Transcription Factors; Forkhead Transcription Factors - genetics; Forkhead Transcription Factors - metabolism; Immune regulation; Immunology; Immunophenotyping; Integrin alpha Chains; Integrin alpha Chains - analysis; Interleukin-2 Receptor alpha Subunit; Interleukin-2 Receptor alpha Subunit - analysis; Langerhans Cells; Langerhans Cells - immunology; Langerhans Cells - metabolism; Lectins, C-Type; Lectins, C-Type - analysis; Life Sciences; Lymph Nodes; Lymph Nodes - immunology; Lymph Nodes - metabolism; Major Histocompatibility Complex; Mannose-Binding Lectins; Mannose-Binding Lectins - analysis; Mice; Mice, Inbred C57BL; Mice, Transgenic; Microscopy, Confocal; NF-kappa B; NF-kappa B - deficiency; NF-kappa B - immunology; Receptors, CCR7; Receptors, CCR7 - analysis; Self Tolerance; Skin; Skin - immunology; T-Lymphocytes, Regulatory; T-Lymphocytes, Regulatory - immunology; T-Lymphocytes, Regulatory - metabolism; Tolerance; Transcription Factor RelB; Transcription Factor RelB - analysis; Transforming Growth Factor beta; Transforming Growth Factor beta - metabolism; Treg cells
• ISSN: 0014-2980; 1521-4141
• DOI: 10.1002/eji.201040930

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 IIint CD86int CD40hi 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.