Lipid droplet-induced T cell death sustains autoimmune tissue inflammation
Year: 2026
Type: article
Abstract: Autoimmunity leading to rheumatoid arthritis (RA) involves CD4 + T cell recruitment into synovial tissue. However, metabolic conditions supporting the survival and pro-inflammatory effector functions of these tissue-invading T cells remain poorly understood. Lipidomic analysis identified the inflamed synovium as a lipid-rich environment. In functional studies, administration of the free fatty acid oleic acid exacerbated synovitis. Tissue-invading CD4 + T cells responded to fatty acid with rapid cell lysis, releasing cytoplasmic and nuclear content into the extracellular space. This T cell lytic death required sequestration of the pore-forming molecule gasdermin D and the acyltransferase zDHHC5 to lipid droplets, which translocated to the plasma membrane to trigger membrane rupture and pyroptotic cell death. Targeting lipid droplet formation in CD4 + T cells through perilipin-2 knockdown or inhibiting gasdermin activation by blocking protein acylation proved highly effective in suppressing synovitis. Thus, autoimmune CD4 + T cells lack metabolic resilience, are primed to undergo pyroptosis in lipid-rich environments, and deliver pro-inflammatory cargo to surrounding tissue.
Source: Cell Metabolism
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: hybrid
Estimated APC paid: $10,400
Awards: DNA Repair and Mitochondrial Dysfunction in T Cell Aging, Influence of Age on CD4 T Memory Cells, Oligoclonal T Cell Expansion and Rheumatoid Arthritis, Mechanisms of genetic variants in TH2 autoimmunity, Memory T Cell Development and Survival in T Cell Responses of Older Individuals, microRNA Regulation of T Cell Senescence, Mitochondrial Malfunction in T Cell Aging and Tissue Inflammation, T Cell Immunity in Giant Cell Arteritis, The NOTCH Signaling Pathway in Large Vessel Vasculitis
OpenAlex ID: W7130309997