TY - JOUR
T1 - Migratory, and not lymphoid-resident, dendritic cells maintain peripheral self-tolerance and prevent autoimmunity via induction of iTreg cells
AU - Vitali, Caterina
AU - Mingozzi, Francesca
AU - Broggi, Achille
AU - Barresi, Simona
AU - Zolezzi, Francesca
AU - Bayry, Jagadeesh
AU - Raimondi, Giorgio
AU - Zanoni, Ivan
AU - Granucci, Francesca
PY - 2012/8/9
Y1 - 2012/8/9
N2 - 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.
AB - 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.
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U2 - 10.1182/blood-2011-09-379776
DO - 10.1182/blood-2011-09-379776
M3 - Article
C2 - 22760781
AN - SCOPUS:84865277279
SN - 0006-4971
VL - 120
SP - 1237
EP - 1245
JO - Blood
JF - Blood
IS - 6
ER -