Journal
JOURNAL OF IMMUNOLOGY
Volume 188, Issue 3, Pages 1108-1116Publisher
AMER ASSOC IMMUNOLOGISTS
DOI: 10.4049/jimmunol.1102084
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Funding
- Ministry of Education, Culture, Sports, Science and Technology of Japan
- Ministry of Health, Labor and Welfare
- National Institute of Biomedical Innovation
- Japan Science and Technology Agency
- Funding Program for Next Generation World-Leading Researchers (NEXT Program)
- Special Coordination Funds for Promoting Science and Technology
- World Class University
- National Research Foundation
- Ministry of Education, Science, and Technology, Korea
- Grants-in-Aid for Scientific Research [11J56423, 11J05843, 23590570] Funding Source: KAKEN
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The intestinal immune system is constantly challenged by commensal bacteria; therefore, it must maintain quiescence via several regulatory mechanisms. Although intestinal macrophages (M phi s) have been implicated in repression of excessive inflammation, it remains unclear how their functions are regulated during inflammation. In this study, we report that semaphorin 7A (Sema7A), a GPI-anchored semaphorin expressed in intestinal epithelial cells (IECs), induces IL-10 production by intestinal M phi s to regulate intestinal inflammation. Sema7A-deficient mice showed severe signs of dextran sodium sulfate-induced colitis due to reduced intestinal IL-10 levels. We further identified CX3CR1(+)MHC class II(int)F4/80(hi)CD11b(hi) M phi s as the main producers of IL-10 via alpha v beta 1 integrin in response to Sema7A. Notably, Sema7A was predominantly expressed on the basolateral side of IECs, and its expression pattern was responsible for protective effects against dextran sodium sulfate-induced colitis and IL-10 production by M phi s during interactions between IECs and M phi s. Furthermore, we determined that the administration of recombinant Sema7A proteins ameliorated the severity of colitis, and these effects were diminished by IL-10-blocking Abs. Therefore, our findings not only indicate that Sema7A plays crucial roles in suppressing intestinal inflammation through alpha v beta 1 integrin, but also provide a novel mode of IL-10 induction via interactions between IECs and M phi s. The Journal of Immunology, 2012, 188: 1108-1116.
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