| First Author | Jones GW | Year | 2011 |
| Journal | FASEB J | Volume | 25 |
| Issue | 1 | Pages | 409-19 |
| PubMed ID | 20826539 | Mgi Jnum | J:167787 |
| Mgi Id | MGI:4880606 | Doi | 10.1096/fj.10-166843 |
| Citation | Jones GW, et al. (2011) Naive and activated T cells display differential responsiveness to TL1A that affects Th17 generation, maintenance, and proliferation. FASEB J 25(1):409-19 |
| abstractText | Tumor necrosis factor (TNF)-like cytokine (TL1A) is a T-cell costimulator that bolsters cytokine-induced activation through death receptor 3 (DR3). To explore the relationship between T-cell activation and TL1A responsiveness, flow cytometry profiled DR3 expression in resting and activated T cells. In human CD4(+) T cells, DR3 was induced rapidly following activation and expressed prominently by interleukin (IL)-17-secreting T cells (Th17). Splenic T cells from wild-type and DR3-deficient mice showed that TL1A activation of DR3 inhibits Th17 generation (81 +/- 2.6% at 100 ng/ml TL1A) from naive T cells. This response was not associated with suppression of T-cell proliferation. Using neutralizing antibodies or T cells derived from genetically modified mice, TL1A inhibition of Th17 development was found to be independent of IL-2, IL-27, gammaIFN, IFNAR1, and STAT1. Under suboptimal TCR activation, TL1A continued to block IL-17A secretion, however, the reduced threshold of TCR engagement was now linked with an increase in TL1A-driven proliferation. In contrast, fully committed Th17 cells displayed an altered TL1A responsiveness and in the absence of TCR costimulation supported the maintenance of T cell IL-17A expression. Consequently, TL1A orchestrates unique outcomes in naive and effector T-helper cells, which may affect the proliferation, differentiation and maintenance of Th17 cells in peripheral compartments and inflamed tissues. |
