| First Author | Landuyt AE | Year | 2019 |
| Journal | J Immunol | Volume | 202 |
| Issue | 4 | Pages | 1039-1044 |
| PubMed ID | 30642977 | Mgi Jnum | J:272885 |
| Mgi Id | MGI:6280739 | Doi | 10.4049/jimmunol.1801266 |
| Citation | Landuyt AE, et al. (2019) Cutting Edge: ICOS-Deficient Regulatory T Cells Display Normal Induction of Il10 but Readily Downregulate Expression of Foxp3. J Immunol 202(4):1039-1044 |
| abstractText | The ICOS pathway has been implicated in the development and functions of regulatory T (Treg) cells, including those producing IL-10. Treg cell-derived IL-10 is indispensable for the establishment and maintenance of intestinal immune homeostasis. We examined the possible involvement of the ICOS pathway in the accumulation of murine colonic Foxp3- and/or IL-10-expressing cells. We show that ICOS deficiency does not impair induction of IL-10 by intestinal CD4 T cells but, instead, triggers substantial reductions in gut-resident and peripherally derived Foxp3(+) Treg cells. ICOS deficiency is associated with reduced demethylation of Foxp3 CNS2 and enhanced loss of Foxp3. This instability significantly limits the ability of ICOS-deficient Treg cells to reverse ongoing inflammation. Collectively, our results identify a novel role for ICOS costimulation in imprinting the functional stability of Foxp3 that is required for the retention of full Treg cell function in the periphery. |
