| First Author | Kawashima H | Year | 2013 |
| Journal | J Immunol | Volume | 191 |
| Issue | 7 | Pages | 3614-23 |
| PubMed ID | 24006461 | Mgi Jnum | J:205943 |
| Mgi Id | MGI:5547455 | Doi | 10.4049/jimmunol.1300509 |
| Citation | Kawashima H, et al. (2013) Tumor suppressor p53 inhibits systemic autoimmune diseases by inducing regulatory T cells. J Immunol 191(7):3614-23 |
| abstractText | The tumor suppressor p53 plays a central role in tumor suppression by inducing apoptosis, cell cycle arrest, senescence, and DNA repair. In addition to the antitumor functions of p53, accumulating evidence using systemic p53-deficient mice suggests that p53 suppresses autoimmunity. However, it remains unknown how p53 suppresses autoimmunity. In this study, we generated T cell-specific p53-deficient mice (CD4-Cre p53(fl/fl) mice, or p53 conditional knockout [cKO] mice) and found that aged p53-cKO mice spontaneously developed inflammatory lesions in various organs, including lung, liver, stomach, thyroid gland, submandibular gland, and kidney. Additionally, anti-nuclear Abs and autoantibodies against gastric parietal cells were detected in p53-cKO mice but not in control p53(fl/fl) mice (p53 wild-type mice). Importantly, the number of Foxp3(+)CD4(+) regulatory T cells (Tregs) in the spleen and lung as well as in vitro differentiation of induced Tregs was significantly reduced in p53-cKO mice as compared with that in p53 wild-type mice. Regarding the mechanisms underlying p53-mediated Treg induction, p53 enhanced the transcription of Foxp3 by binding to the promoter and the conserved noncoding DNA sequence-2 of the Foxp3 gene. Taken together, these results suggest that p53 expressed in T cells functions as a suppressor for autoimmunity by inducing Treg differentiation. |
