Hayashi Fumiaki, Inoue Naoya, Iwatani Yoshinori, Yamashita Yuka, Yamada Hiroya, Miyauchi Akira, Watanabe Mikio
Department of Clinical Laboratory and Biomedical Sciences, The University of Osaka, Graduate School of Medicine, Yamadaoka 1-7 Suita, Osaka 565-0871, Japan.
Kuma Hospital, Kobe, Hyogo 650-0011, Japan.
Immunol Lett. 2025 Dec;276:107036. doi: 10.1016/j.imlet.2025.107036. Epub 2025 May 22.
Regulatory T (Treg) cells, which play an important role in maintaining self-tolerance, are present in the thyroid-infiltrating lymphocytes of patients with autoimmune thyroid disease (AITD). We examined the expression of membrane-bound transforming growth factor-β1 (mTGF-β1), which mediates regulatory function and glucocorticoid-induced tumor necrosis factor receptor-related protein (GITR). The protein in turn may inhibit regulatory function on Treg cells and TGF-β1 receptor II (TGF-βRII) and GITR expression. We also evaluated GITR ligand (GITRL) localization in thyroid tissues. mTGF-β1 cells proportion in Treg cells was higher in the thyroid of patients with AITD than in their peripheral blood. GITR cells proportion among Tregs and Teff cells was also higher in the thyroid than in peripheral blood. GITRL expression in thyrocytes was higher in AITD patients than in healthy subjects. The interaction and balance of mTGF-β1, GITR, TGF-βRII, and GITRL especially thyrocyte GITRL expression, could be critical in AITD pathogenesis.
调节性T(Treg)细胞在维持自身耐受性方面发挥着重要作用,存在于自身免疫性甲状腺疾病(AITD)患者的甲状腺浸润淋巴细胞中。我们检测了介导调节功能的膜结合转化生长因子-β1(mTGF-β1)和糖皮质激素诱导的肿瘤坏死因子受体相关蛋白(GITR)的表达。该蛋白进而可能抑制Treg细胞的调节功能以及TGF-β1受体II(TGF-βRII)和GITR的表达。我们还评估了GITR配体(GITRL)在甲状腺组织中的定位。AITD患者甲状腺中Treg细胞中mTGF-β1细胞比例高于其外周血。甲状腺中Tregs和Teff细胞中GITR细胞比例也高于外周血。AITD患者甲状腺细胞中GITRL表达高于健康受试者。mTGF-β1、GITR、TGF-βRII和GITRL之间的相互作用和平衡,尤其是甲状腺细胞GITRL表达,可能在AITD发病机制中起关键作用。