Migratory, and not lymphoid-resident, dendritic cells maintain peripheral self-tolerance and prevent autoimmunity via induction of iTreg cells

Caterina Vitali, Francesca Mingozzi, Achille Broggi, Simona Barresi, Francesca Zolezzi, Jagadeesh Bayry, Giorgio Raimondi, Ivan Zanoni, Francesca Granucci

Research output: Contribution to journalArticlepeer-review

56 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)1237-1245
Number of pages9
JournalBlood
Volume120
Issue number6
DOIs
StatePublished - Aug 9 2012
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

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