title: Migratory, and not lymphoid-resident, dendritic cells maintain peripheral self-tolerance and prevent autoimmunity via induction of iTreg cells.
abstract: There is evidence that dendritic cells (DCs) induce peripheral tolerance. Nevertheless, it is not known whether immature DCs in general are able to tolerize CD4(+) T cells or if this is a prerogative of specialized subtypes. Here we show that, when autoantigen presentation is extended to all conventional mouse DCs, immature lymphoid tissue resident DCs are unable to induce autoantigen-specific regulatory T (iTreg) cell conversion. In contrast, this is an exclusive prerogative of steady-state migratory DCs. Because only lymph nodes host migratory DCs, iTreg cells develop and are retained solely in lymph nodes, and not in the spleen. Mechanistically, in cutaneous lymph nodes, DC-derived CCL22 contributes to the retention of iTreg cells. The importance of the local generation of iTreg cells is emphasized by their essential role in preventing autoimmunity.
authors: Department of Biotechnology and Biosciences, University of Milano-Bicocca, Milan, Italy.
authors: Caterina
authors: C
authors: Vitali
authors: Francesca
authors: F
authors: Mingozzi
authors: Achille
authors: A
authors: Broggi
authors: Simona
authors: S
authors: Barresi
authors: Francesca
authors: F
authors: Zolezzi
authors: Jagadeesh
authors: J
authors: Bayry
authors: Giorgio
authors: G
authors: Raimondi
authors: Ivan
authors: I
authors: Zanoni
authors: Francesca
authors: F
authors: Granucci
mesh_terms: D000818:Animals; D015551:Autoimmunity / Q000235:genetics / Q000276:immunology / Q000502:physiology; D002465:Cell Movement / Q000235:genetics / Q000502:physiology; D002478:Cells, Cultured; D004268:DNA-Binding Proteins / Q000235:genetics; D003713:Dendritic Cells / Q000378:metabolism / Q000502:physiology*; D005260:Female; D007108:Immune Tolerance / Q000235:genetics / Q000276:immunology / Q000502:physiology*; D008221:Lymphoid Tissue / Q000166:cytology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D008822:Mice, Transgenic; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology* / Q000378:metabolism / Q000502:physiology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000378:metabolism / Q000502:physiology
chemical_list: D004268:DNA-Binding Proteins; C499308:Rag2 protein, mouse