| First Author | Reardon C | Year | 2008 |
| Journal | J Immunol | Volume | 180 |
| Issue | 12 | Pages | 8316-26 |
| PubMed ID | 18523298 | Mgi Jnum | J:137135 |
| Mgi Id | MGI:3798104 | Doi | 10.4049/jimmunol.180.12.8316 |
| Citation | Reardon C, et al. (2008) Transient local depletion of Foxp3(+) regulatory T cells during recovery from colitis via Fas/Fas ligand-induced death. J Immunol 180(12):8316-26 |
| abstractText | Regulatory T cells (T(regs)) play a fundamental role in regulating the immune system in health and disease. Considerable evidence exists demonstrating that transfer of T(regs) can cure colitis and a variety of other inflammatory disorders. However, little is known about the effects of inflammation on resident T(regs). Mice (BALB/c or C57BL/6) treated with an intrarectal instillation of the haptenizing agent 2,4-dinitrobenzene sulfonic acid (DNBS) develop an acute inflammatory disease, the histopathology of which peaks at 3 days posttreatment and resolves spontaneously thereafter. In this study we demonstrate that DNBS (or oxazolone)-induced colitis causes a depletion of colonic Foxp3(+) T(regs) 8 days posttreatment, while the proportion of Foxp3(+) cells in the ileum, mesenteric lymph nodes, and spleen remains unchanged. Replenishment of the colonic T(reg) population was associated with the reappearance of mucosal homing (alpha(4)beta(7)(+)) CD4(+)Foxp3(+) T(regs). Assessing the mechanism of local T(reg) depletion, we found no evidence to implicate cytokine-induced phenotypic switching in the Foxp3(+) population or increased SMAD7 expression despite the essential role that TGF-beta has in Foxp3(+) T(reg) biology. Increased Fas ligand (FasL) expression was observed in the colon of colitic mice and in vitro stimulation with a Fas cross-linking Ab resulted in apoptosis of CD4(+)Foxp3(+) but not CD4(+)Foxp3(-) cells. Furthermore, DNBS-induced colitis in Fas/FasL-deficient mice did not result in depletion of colonic T(regs). Finally, adoptively transferred synergic Fas(-/-) but not Fas(+/+) T(regs) were protected from depletion in the colon 8 days post-DNBS treatment, thus substantiating the hypothesis that inflammation-induced local depletion of Foxp3(+) T(regs) in the colon of mice occurs via Fas/FasL-mediated death. |
