甲状腺功能减退会对免疫系统产生有害影响，但下丘脑-垂体-甲状腺轴在免疫调节和耐受性程序中的确切作用几乎不为人们所了解。本文研究了甲状腺功能减退相关免疫抑制的机制，通过检查HPT轴成分的调节作用。我们首先分析了过表达TRH基因（Tg-Trh）的小鼠的淋巴细胞活动性。 Tg-Trh小鼠的T细胞与野生型（WT）甲状腺正常的小鼠相比对多克隆激活的响应中增加了增殖。 Tg-Trh中Th1类促炎性细胞因子的释放也增加了，并且TSH水平与T细胞增殖相关。为了进一步了解甲状腺功能减退相关的免疫抑制机制，我们评估了甲状腺功能减退和对照小鼠的淋巴组织中的T细胞亚群。这些品系之间的CD3 / CD19或CD4 / CD8比率没有观察到差异。但是，在甲状腺功能减退小鼠中，调节性T细胞（Tregs）的频率显着增加，而在Tg-Trh小鼠中未增加。因此，在甲状腺功能减退小鼠中，体外Tregs分化在未经处理的T细胞中更为明显。由于Tregs过度表达半乳糖凝集素1（Gal-1），缺乏该凝集素（Lgals1-/-）的小鼠显示出降低的Treg功能，因此我们调查了这种免疫调节凝集素在甲状腺功能减退中对Tregs的控制作用。当与甲状腺功能减退WT动物相比较时，在甲状腺功能减退Lgals1-/-小鼠中发现增加的T淋巴细胞反应性和降低的Tregs频率。添加重组Gal-1可恢复此效应。最后，在甲状腺功能减退WT小鼠分离的Tregs中发现Gal-1的表达显著增加。因此，表达Gal-1的Tregs的频率和活性的大量增加是与甲状腺功能减退相关的免疫抑制的根源，这对于免疫病理学，代谢性疾病和癌症具有重要意义。© 2023美国实验生物学会

Hypothyroidism exerts deleterious effects on immunity, but the precise role of the hypothalamic-pituitary-thyroid (HPT) axis in immunoregulatory and tolerogenic programs is barely understood. Here, we investigated the mechanisms underlying hypothyroid-related immunosuppression by examining the regulatory role of components of the HPT axis. We first analyzed lymphocyte activity in mice overexpressing the TRH gene (Tg-Trh). T cells from Tg-Trh showed increased proliferation than wild-type (WT) euthyroid mice in response to polyclonal activation. The release of Th1 pro-inflammatory cytokines was also increased in Tg-Trh and TSH levels correlated with T-cell proliferation. To gain further mechanistic insights into hypothyroidism-related immunosuppression, we evaluated T-cell subpopulations in lymphoid tissues of hypothyroid and control mice. No differences were observed in CD3/CD19 or CD4/CD8 ratios between these strains. However, the frequency of regulatory T cells (Tregs) was significantly increased in hypothyroid mice, and not in Tg-Trh mice. Accordingly, in vitro Tregs differentiation was more pronounced in naïve T cells isolated from hypothyroid mice. Since Tregs overexpress galectin-1 (Gal-1) and mice lacking this lectin (Lgals1-/- ) show reduced Treg function, we investigated the involvement of this immunoregulatory lectin in the control of Tregs in settings of hypothyroidism. Increased T lymphocyte reactivity and reduced frequency of Tregs were found in hypothyroid Lgals1-/- mice when compared to hypothyroid WT animals. This effect was rescued by the addition of recombinant Gal-1. Finally, increased expression of Gal-1 was found in Tregs purified from hypothyroid WT mice compared with their euthyroid counterpart. Thus, a substantial increase in the frequency and activity of Gal-1-expressing Tregs underlies immunosuppression associated with hypothyroid conditions, with critical implications in immunopathology, metabolic disorders, and cancer.© 2023 Federation of American Societies for Experimental Biology.