Impaired expansion of regulatory T cells in a neonatal thymectomy-induced autoimmune mouse model.
Impaired expansion of regulatory T cells in a neonatal thymectomy-induced autoimmune mouse model.
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DOI：
10.1016/j.ajpath.2015.07.007
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发表时间：
2015-11
期刊：
影响因子：
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通讯作者：
A. Yamada;A. Ushio;R. Arakaki;Takaaki Tsunematsu;Y. Kudo;Y. Hayashi;N. Ishimaru
中科院分区：
文献类型：
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作者：
A. Yamada;A. Ushio;R. Arakaki;Takaaki Tsunematsu;Y. Kudo;Y. Hayashi;N. Ishimaru
在某些小鼠品系中，由于T细胞（包括胸腺中的Foxp3+调节性T （Treg）细胞）功能受损，已知新生儿胸腺切除术可诱导器官特异性自身免疫。新生儿胸腺切除术诱导自身免疫的确切机制尚不清楚。一种可能是treg细胞的消耗破坏了外周耐受性。我们通过使用新生胸腺切除术后的NFS/ sld小鼠Sjögren综合征模型来检测Tregcells的功能。胸腺切除小鼠的treg细胞与效应记忆表型T细胞的比例显著低于非胸腺切除小鼠。此外，TGF-β体外诱导外周诱导的TGF-β TGF-β体外诱导Sjögren综合征模型小鼠的treg细胞严重受损。Sjögren综合征模型中TGF-β受体I和II以及TGF-β诱导的Tregcells信号转导通路中Smad3和-4的mRNA表达量低于对照组。此外，Sjögren综合征模型中的treg细胞表现出类似效应T细胞的干扰素-γ产生th1样表型。综上所述，这些结果表明treg细胞的异常扩增和分化以及treg细胞产生的炎症细胞因子参与了自身免疫的发展。
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 Tregcells breaks down peripheral tolerance. We examined the functions of Tregcells by using a murine Sjögren syndrome model of NFS/sldmice that underwent neonatal thymectomy. The ratio of Tregcells to effector memory phenotype T cells in thymectomy mice was significantly lower than that of nonthymectomy mice. In addition,in vitroinduction of peripherally induced Tregcells by transforming growth factor-β (TGF-β) using naive T cells from Sjögren syndrome model mice was severely impaired. The mRNA expression of TGF-β receptor I and II and Smad3 and -4 in the TGF-β–induced signal transduction pathway of Tregcells in this Sjögren syndrome model were lower than those of control mice. In addition, Tregcells in this Sjögren syndrome model exhibited an interferon-γ–producing Th1-like phenotype that resembled effector T cells. In conclusion, these results suggest that abnormal expansion and differentiation of Tregcells and inflammatory cytokines produced by Tregcells contribute to the development of autoimmunity.