| First Author | Yamada A | Year | 2015 |
| Journal | Am J Pathol | Volume | 185 |
| Issue | 11 | Pages | 2886-97 |
| PubMed ID | 26343329 | Mgi Jnum | J:226909 |
| Mgi Id | MGI:5699193 | Doi | 10.1016/j.ajpath.2015.07.007 |
| Citation | Yamada A, et al. (2015) Impaired Expansion of Regulatory T Cells in a Neonatal Thymectomy-Induced Autoimmune Mouse Model. Am J Pathol 185(11):2886-97 |
| abstractText | Neonatal thymectomy in certain mouse strains is known to induce organ-specific autoimmunity due to impaired functions of T cells, including Foxp3(+) regulatory T (Treg) cells in the thymus. The precise mechanism underlying the induction of autoimmunity by neonatal thymectomy remains unclear. One possibility is that depletion of Treg cells breaks down peripheral tolerance. We examined the functions of Treg cells by using a murine Sjogren syndrome model of NFS/sld mice that underwent neonatal thymectomy. The ratio of Treg cells to effector memory phenotype T cells in thymectomy mice was significantly lower than that of nonthymectomy mice. In addition, in vitro induction of peripherally induced Treg cells by transforming growth factor-beta (TGF-beta) using naive T cells from Sjogren syndrome model mice was severely impaired. The mRNA expression of TGF-beta receptor I and II and Smad3 and -4 in the TGF-beta-induced signal transduction pathway of Treg cells in this Sjogren syndrome model were lower than those of control mice. In addition, Treg cells in this Sjogren syndrome model exhibited an interferon-gamma-producing Th1-like phenotype that resembled effector T cells. In conclusion, these results suggest that abnormal expansion and differentiation of Treg cells and inflammatory cytokines produced by Treg cells contribute to the development of autoimmunity. |
