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A Protective Role for Human IL-10–Expressing CD4+ T Cells in Colitis

Authors :
Priyanka Uprety
Jay H. Bream
Dilini Ranatunga
Joseph B. Margolick
Amritha Ramakrishnan
Fengying Wang
Cory Brayton
Hao Zhang
Source :
The Journal of Immunology. 189:1243-1252
Publication Year :
2012
Publisher :
The American Association of Immunologists, 2012.

Abstract

IL-10 is an immunoregulatory cytokine expressed by numerous cell types. Studies in mice confirm that different IL-10–expressing cell subsets contribute differentially to disease phenotypes. However, little is known about the relationship between cell- or tissue-specific IL-10 expression and disease susceptibility in humans. In this study, we used the previously described human (h)IL10BAC transgenic model to examine the role of hIL-10 in maintaining intestinal homeostasis. Genomically controlled hIL-10 expression rescued Il10−/− mice from Helicobacter-induced colitis and was associated with control of proinflammatory cytokine expression and Th17 cell accumulation in gut tissues. Resistance to colitis was associated with an accumulation of hIL-10–expressing CD4+Foxp3+ regulatory T cells specifically within the lamina propria but not other secondary lymphoid tissues. Cotransfer of CD4+CD45RBlo cells from Il10−/−/hIL10BAC mice rescued Rag1−/− mice from colitis, further suggesting that CD4+ T cells represent a protective source of hIL-10 in the colon. In concordance with an enhanced capacity to express IL-10, CD4+CD44+ T cells isolated from the lamina propria exhibited lower levels of the repressive histone mark H3K27Me3 and higher levels of the permissive histone mark acetylated histone H3 in both the human and mouse IL10 locus compared with the spleen. These results provide experimental evidence verifying the importance of T cell-derived hIL-10 expression in controlling inflammation within the colonic mucosa. We also provide molecular evidence suggesting the tissue microenvironment influences IL-10 expression patterns and chromatin structure in the human (and mouse) IL10 locus.

Details

ISSN :
15506606 and 00221767
Volume :
189
Database :
OpenAIRE
Journal :
The Journal of Immunology
Accession number :
edsair.doi.dedup.....0984416a2a887ab9eba57d2d5476e52c