| First Author | Costes LMM | Year | 2019 |
| Journal | Mucosal Immunol | Volume | 12 |
| Issue | 2 | Pages | 479-490 |
| PubMed ID | 30542112 | Mgi Jnum | J:295149 |
| Mgi Id | MGI:6459691 | Doi | 10.1038/s41385-018-0118-0 |
| Citation | Costes LMM, et al. (2019) IL-10 signaling prevents gluten-dependent intraepithelial CD4(+) cytotoxic T lymphocyte infiltration and epithelial damage in the small intestine. Mucosal Immunol 12(2):479-490 |
| abstractText | Breach of tolerance to gluten leads to the chronic small intestinal enteropathy celiac disease. A key event in celiac disease development is gluten-dependent infiltration of activated cytotoxic intraepithelial lymphocytes (IELs), which cytolyze epithelial cells causing crypt hyperplasia and villous atrophy. The mechanisms leading to gluten-dependent small intestinal IEL infiltration and activation remain elusive. We have demonstrated that under homeostatic conditions in mice, gluten drives the differentiation of anti-inflammatory T cells producing large amounts of the immunosuppressive cytokine interleukin-10 (IL-10). Here we addressed whether this dominant IL-10 axis prevents gluten-dependent infiltration of activated cytotoxic IEL and subsequent small intestinal enteropathy. We demonstrate that IL-10 regulation prevents gluten-induced cytotoxic inflammatory IEL infiltration. In particular, IL-10 suppresses gluten-induced accumulation of a specialized population of cytotoxic CD4(+)CD8alphaalpha(+) IEL (CD4(+) CTL) expressing Tbx21, Ifng, and Il21, and a disparate non-cytolytic CD4(+)CD8alpha(-) IEL population expressing Il17a, Il21, and Il10. Concomitantly, IL-10 suppresses gluten-dependent small intestinal epithelial hyperproliferation and upregulation of stress-induced molecules on epithelial cells. Remarkably, frequencies of granzyme B(+)CD4(+)CD8alpha(+) IEL are increased in pediatric celiac disease patient biopsies. These findings demonstrate that IL-10 is pivotal to prevent gluten-induced small intestinal inflammation and epithelial damage, and imply that CD4(+) CTL are potential new players into these processes. |
