| First Author | Gao Y | Year | 2025 |
| Journal | Science | Volume | 390 |
| Issue | 6769 | Pages | eadt4169 |
| PubMed ID | 41066556 | Mgi Jnum | J:373127 |
| Mgi Id | MGI:8250909 | Doi | 10.1126/science.adt4169 |
| Citation | Gao Y, et al. (2025) T cell cholesterol transport links intestinal immune responses to dietary lipid absorption. Science 390(6769):eadt4169 |
| abstractText | 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 (Ca(2+)) flux. Aster-A deficiency promoted CD4 T cells to acquire a T helper 17 (T(H)17) 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. |
