大阪大学Shimon Sakaguchi小组近日取得一项新成果。经过不懈努力，他们的论文发现了可溶性CTLA-4调节免疫稳态，通过抑制1型而允许2型免疫来促进炎症的解决。相关论文发表在2025年3月31日出版的《免疫学》杂志上。

研究小组研究了sCTLA-4在非炎症和炎症条件下的免疫调节中的作用。在基础状态和炎症状态下，效应调节性T细胞（Treg）是最活跃的sCTLA-4产生细胞，在T细胞受体（TCR）刺激下具有不同的动力学。小组培育了sCTLA-4产生特异性缺陷的小鼠，这些小鼠表现出1型免疫细胞的自发激活和自身抗体/免疫球蛋白E （IgE）产生的增加。相反，mCTLA-4缺陷小鼠出现严重的2型倾斜自身免疫。sCTLA-4阻断抗原呈递细胞的CD80/86可抑制体外辅助性T (Th)1的分化，但不抑制Th2的分化。在体内，treg产生sCTLA-4，抑制th1介导的实验性结肠炎，促进伤口愈合，但阻碍肿瘤免疫。因此，sCTLA-4对于免疫稳态和控制1型免疫至关重要，同时允许2型免疫促进炎症条件的解决。

据介绍，细胞毒性T淋巴细胞相关抗原-4 （CTLA-4）是一种限制T细胞活化的共抑制受体。CTLA-4以膜（mCTLA-4）和可溶性（sCTLA-4）两种形式存在，但主要的产生物、动力学和功能尚不清楚。

附：英文原文

Title: Soluble CTLA-4 regulates immune homeostasis and promotes resolution of inflammation by suppressing type 1 but allowing type 2 immunity

Author: Motonao Osaki, Shimon Sakaguchi

Issue&Volume: 2025-03-31

Abstract: Cytotoxic T-lymphocyte-associated antigen -4 (CTLA-4) is a co-inhibitory receptor that restricts T cell activation. CTLA-4 exists as membrane (mCTLA-4) and soluble (sCTLA-4) forms, but the key producers, kinetics, and functions of sCTLA-4 are unclear. Here, we investigated the roles of sCTLA-4 in immune regulation under non-inflammatory and inflammatory conditions. Effector regulatory T (Treg) cells were the most active sCTLA-4 producers in basal and inflammatory states, with distinct kinetics upon T cell receptor (TCR) stimulation. We generated mice specifically deficient in sCTLA-4 production, which exhibited spontaneous activation of type 1 immune cells and heightened autoantibody/immunoglobulin E (IgE) production. Conversely, mCTLA-4-deficient mice developed severe type 2-skewed autoimmunity. sCTLA-4 blockade of CD80/86 on antigen-presenting cells inhibited T helper (Th)1, but not Th2, differentiation in vitro. In vivo, Treg-produced sCTLA-4, suppressed Th1-mediated experimental colitis, and enhanced wound healing but hampered tumor immunity. Thus, sCTLA-4 is essential for immune homeostasis and controlling type 1 immunity while allowing type 2 immunity to facilitate resolution in inflammatory conditions.

DOI: 10.1016/j.immuni.2025.03.004

Source: https://www.cell.com/immunity/abstract/S1074-7613(25)00123-2