Prostaglandin E2 and SOCS1 have a role in intestinal immune tolerance
Copyright policy )Prostaglandin E2 and SOCS1 have a role in intestinal immune tolerance
Interleukin 10 (IL-10) and regulatory T cells (Tregs) maintain tolerance to intestinal microorganisms. However, Il10(-/-)Rag2(-/-) mice, which lack IL-10 and Tregs, remain healthy, suggesting the existence of other mechanisms of tolerance. Here, we identify suppressor of cytokine signalling 1 (SOCS1) as an essential mediator of immune tolerance in the intestine. Socs1(-/-)Rag2(-/-) mice develop severe colitis, which can be prevented by the reduction of microbiota and the transfer of IL-10-sufficient Tregs. Additionally, we find an essential role for prostaglandin E2 (PGE2) in the maintenance of tolerance within the intestine in the absence of Tregs. Socs1(-/-) dendritic cells are resistant to PGE2-mediated immunosuppression because of dysregulated cytokine signalling. Thus, we propose that SOCS1 and PGE2, potentially interacting together, act as an alternative intestinal tolerance mechanism distinct from IL-10 and Tregs.
- Japan Science and Technology Agency Japan
- Kyushu University Japan
- Keio University Japan
Mice, Knockout, Indomethacin, Enzyme-Linked Immunosorbent Assay, Suppressor of Cytokine Signaling Proteins, Flow Cytometry, T-Lymphocytes, Regulatory, Article, Dinoprostone, Interleukin-10, DNA-Binding Proteins, Intestines, Mice, Suppressor of Cytokine Signaling 1 Protein, Immune Tolerance, Animals
Mice, Knockout, Indomethacin, Enzyme-Linked Immunosorbent Assay, Suppressor of Cytokine Signaling Proteins, Flow Cytometry, T-Lymphocytes, Regulatory, Article, Dinoprostone, Interleukin-10, DNA-Binding Proteins, Intestines, Mice, Suppressor of Cytokine Signaling 1 Protein, Immune Tolerance, Animals
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