Division of Translational Medicine, Research Branch, Sidra Medical and Research Center, P.O. Box 26999, Doha, Qatar.
Division of Translational Medicine, Research Branch, Sidra Medical and Research Center, P.O. Box 26999, Doha, Qatar.
Curr Opin Immunol. 2017 Dec;49:14-19. doi: 10.1016/j.coi.2017.07.014. Epub 2017 Aug 11.
CTLA-4 is a crucial negative regulator of immune responses. Absence of CTLA-4 in mice causes autoimmunity and lethal multiorgan lymphocytic infiltration and tissue destruction. Recently, heterozygous CTLA4 or biallelic LRBA mutations leading to functional CTLA-4 deficiency and autoimmunity have been discovered. LRBA was identified as a novel regulator of steady-state CTLA-4 protein levels in Tregs and activated T cells. CTLA-4 deficiency due to checkpoint blockade cancer immunotherapy has also been found to lead to autoimmune reactions. Studies investigating the variable efficacy and adverse autoimmune responses to checkpoint therapy elucidated a role of the microbiota in promoting antitumor and autoreactive immune responses that are regulated by CTLA-4.
CTLA-4 是免疫反应的关键负调节剂。CTLA-4 在小鼠中的缺失会导致自身免疫以及致命的多器官淋巴细胞浸润和组织破坏。最近，已发现杂合性 CTLA4 或双等位基因 LRBA 突变导致功能性 CTLA-4 缺乏和自身免疫。LRBA 被鉴定为 Tregs 和激活的 T 细胞中稳态 CTLA-4 蛋白水平的新型调节剂。由于检查点阻断癌症免疫疗法导致的 CTLA-4 缺乏也被发现会导致自身免疫反应。研究检查点治疗的可变疗效和不良反应性自身免疫反应表明，微生物群在促进由 CTLA-4 调节的抗肿瘤和自身反应性免疫反应中起作用。
