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Toll-like receptor 2-dependent induction of vitamin A-metabolizing enzymes in dendritic cells promotes T regulatory responses and inhibits autoimmunity.

ABSTRACT: Immune sensing of a microbe occurs via multiple receptors. How signals from different receptors are coordinated to yield a specific immune response is poorly understood. We show that two pathogen recognition receptors, Toll-like receptor 2 (TLR2) and dectin-1, recognizing the same microbial stimulus, stimulate distinct innate and adaptive responses. TLR2 signaling induced splenic dendritic cells (DCs) to express the retinoic acid metabolizing enzyme retinaldehyde dehydrogenase type 2 and interleukin-10 (IL-10) and to metabolize vitamin A and stimulate Foxp3(+) T regulatory cells (T(reg) cells). Retinoic acid acted on DCs to induce suppressor of cytokine signaling-3 expression, which suppressed activation of p38 mitogen-activated protein kinase and proinflammatory cytokines. Consistent with this finding, TLR2 signaling induced T(reg) cells and suppressed IL-23 and T helper type 17 (T(H)17) and T(H)1-mediated autoimmune responses in vivo. In contrast, dectin-1 signaling mostly induced IL-23 and proinflammatory cytokines and augmented T(H)17 and T(H)1-mediated autoimmune responses in vivo. These data define a new mechanism for the systemic induction of retinoic acid and immune suppression against autoimmunity.

SUBMITTER: Manicassamy S

PROVIDER: S-EPMC2768543 | biostudies-literature | 2009 Apr

REPOSITORIES: biostudies-literature

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Toll-like receptor 2-dependent induction of vitamin A-metabolizing enzymes in dendritic cells promotes T regulatory responses and inhibits autoimmunity.

Manicassamy Santhakumar S Ravindran Rajesh R Deng Jiusheng J Oluoch Herold H Denning Timothy L TL Kasturi Sudhir Pai SP Rosenthal Kristen M KM Evavold Brian D BD Pulendran Bali B

Nature medicine 20090301 4

Immune sensing of a microbe occurs via multiple receptors. How signals from different receptors are coordinated to yield a specific immune response is poorly understood. We show that two pathogen recognition receptors, Toll-like receptor 2 (TLR2) and dectin-1, recognizing the same microbial stimulus, stimulate distinct innate and adaptive responses. TLR2 signaling induced splenic dendritic cells (DCs) to express the retinoic acid metabolizing enzyme retinaldehyde dehydrogenase type 2 and interle ...[more]

PMID: 19252500

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Dataset Information

Toll-like receptor 2-dependent induction of vitamin A-metabolizing enzymes in dendritic cells promotes T regulatory responses and inhibits autoimmunity.

Publications

Toll-like receptor 2-dependent induction of vitamin A-metabolizing enzymes in dendritic cells promotes T regulatory responses and inhibits autoimmunity.

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