First Author | Li L | Year | 2016 |
Journal | Cell Death Dis | Volume | 7 |
Issue | 10 | Pages | e2439 |
PubMed ID | 27787514 | Mgi Jnum | J:328776 |
Mgi Id | MGI:6851365 | Doi | 10.1038/cddis.2016.348 |
Citation | Li L, et al. (2016) Block of both TGF-beta and IL-2 signaling impedes Neurophilin-1(+) regulatory T cell and follicular regulatory T cell development. Cell Death Dis 7(10):e2439 |
abstractText | Understanding the mechanisms that lead to autoimmunity is critical for defining potential therapeutic pathways. In this regard there have been considerable efforts in investigating the interacting roles of TGF-beta and IL-2 on the function regulatory T cells. We have taken advantage of dnTGF-betaRII Il2ra(-/-) (abbreviated as Il2ra(-/-)Tg) mouse model, which allows a direct mechanistic approach to define the relative roles of TGF-beta and IL-2 on Treg development. Il2ra(-/-)Tg mice spontaneously developed multi-organ autoimmune diseases with expansion of pathogenic T cells and enhanced germinal center response at 3-4 weeks of age. Importantly, peripheral Treg cells from Il2ra(-/-)Tg mice demonstrated an activated Th1-like stable phenotype and normal in vitro suppressive function, while thymus Treg increased but manifested decreased suppressive function. Interestingly, neither thymus nor peripheral Treg cells of Il2ra(-/-)Tg mice contained Neuropilin-1(+) or PD-1(hi) phenotype, resulting in defective follicular regulatory T (Tfr) cell development. Such defective Tfr development led to elevated follicular T helper cells, enhanced germinal center responses and increased plasma cell infiltration. These data demonstrate an important synergetic role of TGF-beta and IL-2 in the generation, activation and stability of Treg cells, as well as their subsequent development into Tfr cells. |