T cell cholesterol transport is a metabolic checkpoint that links intestinal immune responses to dietary lipid absorption 2108
Year: 2025
Type: article
Abstract: Description The intrinsic pathways that control membrane organization in immune cells and the impact of such pathways on cellular function are not well defined. Here we report that the non-vesicular cholesterol transporter Aster-A links plasma membrane (PM) cholesterol availability in T cells to immune signaling and systemic metabolism. Aster-A is recruited to the PM during T-cell receptor (TCR) activation, where it facilitates the removal of newly generated “accessible” membrane cholesterol. Loss of Aster-A leads to excess PM cholesterol accumulation, resulting in enhanced TCR nano-clustering and signaling, and Th17 cytokine production. Finally, we show that the mucosal Th17 response is restrained by PM cholesterol remodeling. Ablation of Aster-A in T cells leads to enhanced IL-22 production, reduced intestinal fatty acid absorption, and resistance to diet-induced obesity. These findings delineate a multi-tiered regulatory scheme linking immune cell lipid flux to nutrient absorption and systemic physiology. Funding Sources Supported by Damon Runyon Foundation/The Mark Foundation Postdoctoral Fellowship DRG-2424-21 and NIH/NCATS UL1TR001881; AHA Postdoctoral Fellowship 903306 and 18POST34030388; NIH CDI K12 07012023; ADA Postdoctoral fellowship 1-19-PDF-043-RA; NIH T32 DK007180 and K08DK136706; NIH F30 DK134050; NIH R01 DK126779, R01 HL175773, and Leducq Foundation Transatlantic Network of Excellence 19CDV04. Topic Categories Mucosal and Regional Immunology (MUC)
Source: The Journal of Immunology
Authors: Yajing Gao, John Paul Kennelly, Peter Tontonoz
Institution: University of California, Los Angeles
Language: English
Subfield: Surgery
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
OpenAlex ID: W4416449404
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