| First Author | Holmkvist P | Year | 2016 |
| Journal | Eur J Immunol | Volume | 46 |
| Issue | 6 | Pages | 1371-82 |
| PubMed ID | 27062602 | Mgi Jnum | J:246483 |
| Mgi Id | MGI:5923818 | Doi | 10.1002/eji.201545957 |
| Citation | Holmkvist P, et al. (2016) IL-18Ralpha-deficient CD4(+) T cells induce intestinal inflammation in the CD45RB(hi) transfer model of colitis despite impaired innate responsiveness. Eur J Immunol 46(6):1371-82 |
| abstractText | IL-18 has been implicated in inflammatory bowel disease (IBD), however its role in the regulation of intestinal CD4(+) T-cell function remains unclear. Here we show that murine intestinal CD4(+) T cells express high levels of IL-18Ralpha and provide evidence that IL-18Ralpha expression is induced on these cells subsequent to their entry into the intestinal mucosa. Using the CD45RB(hi) T-cell transfer colitis model, we show that IL-18Ralpha is expressed on IFN-gamma(+) , IL-17(+) , and IL-17(+) IFN-gamma(+) effector CD4(+) T cells in the inflamed colonic lamina propria (cLP) and mesenteric lymph node (MLN) and is required for the optimal generation and/or maintenance of IFN-gamma-producing cells in the cLP. In the steady state and during colitis, TCR-independent cytokine-induced IFN-gamma and IL-17 production by intestinal CD4(+) T cells was largely IL-18Ralpha-dependent. Despite these findings however, IL-18Ralpha-deficient CD4(+) T cells induced comparable intestinal pathology to WT CD4(+) T cells. These findings suggest that IL-18-dependent cytokine induced activation of CD4(+) T cells is not critical for the development of T-cell-mediated colitis. |
