Singapore Immunology Network (SIgN), Agency for Science, Technology and Research (ASTAR), Singapore, Singapore.
Department of Infection, Immunity and Cardiovascular Diseases, The University of Sheffield, Sheffield, United Kingdom.
Front Immunol. 2019 Jul 15;10:1566. doi: 10.3389/fimmu.2019.01566. eCollection 2019.
The inflammasome is a multi-protein complex that mediates proteolytic cleavage and release of the pro-inflammatory cytokines IL-1β and IL-18, and pyroptosis-a form of cell death induced by various pathogenic bacteria. Apoptosis-associated speck-like protein containing a CARD (ASC) has a pivotal role in inflammasome assembly and activation. While ASC function has been primarily implicated in innate immune cells, its contribution to lymphocyte biology is unclear. Here we report that ASC is constitutively expressed in naïve CD4 T cells together with the inflammasome sensor NLRP3 and caspase-1. When adoptively transferred in immunocompromised Rag1 mice, Asc CD4 T cells exacerbate T-cell-mediated autoimmune colitis. Asc CD4 T cells exhibit a higher proliferative capacity than wild-type CD4 T cells. The increased expansion of Asc CD4 T cells correlated with robust TCR-mediated activation, inflammatory activity, and higher metabolic profile toward a highly glycolytic phenotype. These findings identify ASC as a crucial intrinsic regulator of CD4 T-cell expansion that serves to maintain intestinal homeostasis.
炎症小体是一种多蛋白复合物，介导促炎细胞因子 IL-1β 和 IL-18 的蛋白水解切割和释放，以及焦亡——一种由各种病原细菌诱导的细胞死亡形式。含有 CARD（ASC）的凋亡相关斑点样蛋白在炎症小体组装和激活中起着关键作用。虽然 ASC 的功能主要涉及先天免疫细胞，但它对淋巴细胞生物学的贡献尚不清楚。在这里，我们报告 ASC 与炎症小体传感器 NLRP3 和 caspase-1 一起在幼稚 CD4 T 细胞中持续表达。当过继转移到免疫缺陷 Rag1 小鼠中时，Asc CD4 T 细胞加剧了 T 细胞介导的自身免疫性结肠炎。与野生型 CD4 T 细胞相比，Asc CD4 T 细胞具有更高的增殖能力。Asc CD4 T 细胞的扩增增加与强烈的 TCR 介导的激活、炎症活性以及向高度糖酵解表型的更高代谢特征相关。这些发现确定 ASC 是 CD4 T 细胞扩增的关键内在调节因子，有助于维持肠道内稳态。
