Mechanism of autoimmune tissue inflammation in rheumatoid arthritis

It is well known that synovial tissue of rheumatoid arthritis (RA) contain CD4⁺ T cell  but their role in pro-inflammatory functions is not well understood.

The researchers in this study identify a metabolically controlled trait of CD4+ T cells in autoimmune disease.

Exposed to fatty acids in rheumatoid joints, they form lipid droplets containing pore-forming gasdermin D and its activator zDHHC5 which translocated to the plasma membrane to trigger membrane rupture and pyroptotic cell death resulting in the leakage of intracellular contents and tissue inflammation.

The authors show that 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.

https://www.cell.com/cell-metabolism/fulltext/S1550-4131(26)00015-X

https://sciencemission.com/Lipid-droplet-induced-T-cell-death