美国国立卫生研究院Claudia Kemper、Erin E. West研究组的最新研究发现，CD4⁺ T细胞内在精氨酸酶1（Arg1）缺失会加速Th1反应动力学并减少流感感染时肺部病理的产生。这一研究成果于2023年8月11日发表在国际学术期刊《免疫》上。

研究人员证明小鼠感染流感时Arg1的诱导表达是肺CD4⁺ T细胞的关键特征。CD4⁺ T细胞中Arg1的条件性缺失加速了病毒特异性辅助性T1（Th1）效应子的反应及消退，从而有效地清除病毒并减少肺部病理。使用无偏倚转录组学和代谢组学，研究发现Arg1缺乏与Arg2缺乏不同，并导致谷氨酰胺代谢改变。重新平衡谷氨酰胺通量的波动可使细胞Th1反应正常化。来自罕见ARG1缺陷患者的CD4⁺ T细胞或在健康供体细胞中使用CRISPR-Cas9介导ARG1缺失的表型重现了小鼠细胞表型。

总的来说，CD4⁺ T细胞内在Arg1是一种意想不到的变阻器，调节哺乳动物Th1生命周期动力学并对Th1相关组织病理产生影响。

据悉，精氨酸酶1是催化精氨酸转化为鸟氨酸的酶，是M2巨噬细胞产生IL-10免疫调节因子的标志。然而，它在T细胞中的表达存在争议的。

附：英文原文

Title: Loss of CD4+ T cell-intrinsic arginase 1 accelerates Th1 response kinetics and reduces lung pathology during influenza infection

Author: Erin E. West, Nicolas S. Merle, Marcin M. Kamiński, Gustavo Palacios, Dhaneshwar Kumar, Luopin Wang, Jack A. Bibby, Kirsten Overdahl, Alan K. Jarmusch, Simon Freeley, Duck-Yeon Lee, J. Will Thompson, Zu-Xi Yu, Naomi Taylor, Marc Sitbon, Douglas R. Green, Andrea Bohrer, Katrin D. Mayer-Barber, Behdad Afzali, Majid Kazemian, Sabine Scholl-Buergi, Daniela Karall, Martina Huemer, Claudia Kemper

Issue&Volume: 2023-08-11

Abstract: Arginase 1 (Arg1), the enzyme catalyzing the conversion of arginine to ornithine, is a hallmark of IL-10-producing immunoregulatory M2 macrophages. However, its expression in T cells is disputed. Here, we demonstrate that induction of Arg1 expression is a key feature of lung CD4+ T cells during mouse in vivo influenza infection. Conditional ablation of Arg1 in CD4+ T cells accelerated both virus-specific T helper 1 (Th1) effector responses and its resolution, resulting in efficient viral clearance and reduced lung pathology. Using unbiased transcriptomics and metabolomics, we found that Arg1-deficiency was distinct from Arg2-deficiency and caused altered glutamine metabolism. Rebalancing this perturbed glutamine flux normalized the cellular Th1 response. CD4+ T cells from rare ARG1-deficient patients or CRISPR-Cas9-mediated ARG1-deletion in healthy donor cells phenocopied the murine cellular phenotype. Collectively, CD4+ T cell-intrinsic Arg1 functions as an unexpected rheostat regulating the kinetics of the mammalian Th1 lifecycle with implications for Th1-associated tissue pathologies.

DOI: 10.1016/j.immuni.2023.07.014

Source: https://www.cell.com/immunity/fulltext/S1074-7613(23)00327-8