该课题组人员发现非囊性胆固醇转运体Aster-A与CD4 T细胞中质膜（PM）胆固醇的可用性有关。在T细胞受体（TCR）激活过程中，Aster-A被招募到PM，在那里它促进了可接近胆固醇的去除。Aster-A的缺失增加了PM中胆固醇的积累，从而增强了TCR纳米化和信号传导。Aster-A与基质相互作用分子1 （STIM1）相关，负调控钙（Ca2+）通量。Aster-A缺乏促进CD4 T细胞获得辅助性T细胞17 （TH17）表型并刺激白细胞介素22的产生，从而减少肠道脂肪吸收并赋予对饮食性肥胖的抵抗力。这些发现描述了免疫细胞膜稳态与全身生理的联系。
研究人员表示，控制免疫细胞膜组织的内在途径及其对细胞功能的影响尚不清楚。
附：英文原文
Title: T cell cholesterol transport links intestinal immune responses to dietary lipid absorption
Author: Yajing Gao, John P. Kennelly, Xu Xiao, Emily Whang, Alessandra Ferrari, Alexander H. Bedard, Julia J. Mack, Alexander Nguyen, Sonal Srikanth, Thomas Weston, Lauren F. Uchiyama, Whitaker Cohn, Danielle H. Cho, Min Sub Lee, Julian Whitelegge, Yousang Gwack, Stephen G. Young, Steven J. Bensinger, Peter Tontonoz
Issue&Volume: 2025-10-09
Abstract: The intrinsic pathways that control membrane organization in immune cells and their impact on cellular functions are poorly defined. We found that the nonvesicular cholesterol transporter Aster-A linked plasma membrane (PM) cholesterol availability in CD4 T cells to systemic metabolism. Aster-A was recruited to the PM during T cell receptor (TCR) activation, where it facilitated the removal of accessible cholesterol. Loss of Aster-A increased cholesterol accumulation in the PM, which enhanced TCR nanoclustering and signaling. Aster-A associated with stromal interaction molecule 1 (STIM1) and negatively regulated calcium (Ca2+) flux. Aster-A deficiency promoted CD4 T cells to acquire a T helper 17 (TH17) phenotype and stimulated interleukin-22 production, which reduced intestinal fat absorption and conferred resistance to diet-induced obesity. These findings delineate how immune cell membrane homeostasis links to systemic physiology.
DOI: adt4169
Source: https://www.science.org/doi/10.1126/science.adt4169