T cell cholesterol transport links intestinal immune responses to dietary lipid absorption.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 41066556.
- Also identified by DOI 10.1126/science.adt4169 and PMC identifier 13034976.
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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 (Ca<sup>2+</sup>) flux. Aster-A deficiency promoted CD4 T cells to acquire a T helper 17 (T<sub>H</sub>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.
Medical subject headings
- Cholesterol
- Intestinal Absorption
- CD4-Positive T-Lymphocytes
- Th17 Cells
- Dietary Fats
- Intestinal Mucosa