| First Author | Hang L | Year | 2019 |
| Journal | J Immunol | Volume | 202 |
| Issue | 8 | Pages | 2473-2481 |
| PubMed ID | 30850474 | Mgi Jnum | J:274563 |
| Mgi Id | MGI:6287915 | Doi | 10.4049/jimmunol.1801392 |
| Citation | Hang L, et al. (2019) Heligmosomoides polygyrus bakeri Infection Decreases Smad7 Expression in Intestinal CD4(+) T Cells, Which Allows TGF-beta to Induce IL-10-Producing Regulatory T Cells That Block Colitis. J Immunol 202(8):2473-2481 |
| abstractText | Helminthic infections modulate host immunity and may protect their hosts from developing immunological diseases like inflammatory bowel disease. Induction of regulatory T cells (Tregs) may be an important part of this protective process. Heligmosomoides polygyrus bakeri infection also promotes the production of the regulatory cytokines TGF-beta and IL-10 in the gut. In the intestines, TGF-beta helps induce regulatory T cells. This study used Foxp3/IL-10 double reporter mice to investigate the effect of TGF-beta on the differentiation of colon and mesenteric lymph node-derived murine Foxp3(-) IL-10(-) CD4(+) T cells into their regulatory phenotypes. Foxp3(-) IL-10(-) CD4(+) T cells from H. polygyrus bakeri-infected mice, as opposed to T cells from uninfected animals, cultured in vitro with TGF-beta and anti-CD3/CD28 mAb differentiated into Foxp3(+) and/or IL-10(+) T cells. The IL-10-producing T cells nearly all displayed CD25. Smad7 is a natural inhibitor of TGF-beta signaling. In contrast to gut T cells from uninfected mice, Foxp3(-) IL10(-) CD4(+) T cells from H. polygyrus bakeri-infected mice displayed reduced Smad7 expression and responded to TGF-beta with Smad2/3 phosphorylation. The TGF-beta-induced Tregs that express IL-10 blocked colitis when transferred into the Rag/CD25(-) CD4(+) T cell transfer model of inflammatory bowel disease. TGF-beta had a greatly diminished capacity to induce Tregs in H. polygyrus bakeri-infected transgenic mice with constitutively high T cell-specific Smad7 expression. Thus, infection with H. polygyrus bakeri causes down-modulation in Smad7 expression in intestinal CD4(+) T cells, which allows the TGF-beta produced in response to the infection to induce the Tregs that prevent colitis. |
