IL-10 is an immunomodulatory cytokine that plays an obligate role in preventing spontaneous enterocolitis in mice. However, little is known about IL-10 function in the human intestinal mucosa. We showed here that IL-10 was constitutively expressed and secreted by the human normal colonic mucosa, including epithelial cells. Depletion of IL-10 in mucosal explants induced both downregulation of the IL-10–inducible, immunosuppressive gene BCL3 and upregulation of IFN-γ, TNF-α, and IL-17. Interestingly, TGF-β blockade also strongly induced IFN-γ production. In addition, the high levels of IFN-γ produced upon IL-10 depletion were responsible for surface epithelium damage and crypt loss, mainly by apoptosis. Polymyxin B, used as a scavenger of endogenous LPS, abolished both IFN-γ production and epithelial barrier disruption. Finally, adding a commensal bacteria strain to mucosa explant cultures depleted of both IL-10 and LPS reproduced the ability of endogenous LPS to induce IFN-γ secretion. These findings demonstrate that IL-10 ablation leads to an endogenous IFN-γ–mediated inflammatory response via LPS from commensal bacteria in the human colonic mucosa. We also found that both IL-10 and TGF-β play crucial roles in maintaining human colonic mucosa homeostasis.
Anne Jarry, Céline Bossard, Chantal Bou-Hanna, Damien Masson, Eric Espaze, Marc G. Denis, Christian L. Laboisse
Title and authors | Publication | Year |
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IFN-γ-Mediated Induction of an Apical IL-10 Receptor on Polarized Intestinal Epithelia
DJ Kominsky, EL Campbell, SF Ehrentraut, KE Wilson, CJ Kelly, LE Glover, CB Collins, AJ Bayless, B Saeedi, E Dobrinskikh, BE Bowers, CF Macmanus, W Müller, SP Colgan, D Bruder |
Journal of immunology (Baltimore, Md. : 1950) | 2013 |
Pathogenesis of Human Enterovirulent Bacteria: Lessons from Cultured, Fully Differentiated Human Colon Cancer Cell Lines
VL Moal, AL Servin |
Microbiology and molecular biology reviews : MMBR | 2013 |
Interleukin-10 prevents epithelial cell apoptosis by regulating IFNγ and TNFα expression in rhesus macaque colon explants
D Pan, A Das, W Lala, CS Kenway-Lynch, DX Liu, RS Veazey, B Pahar |
Cytokine | 2013 |