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CD38 controls IL-2 production in CD4 T cells

GSE273009 Homo sapiens Expression profiling by high throughput sequencing 6 samples Submitted 2024/10/15 Platform GPL18573
Summary
CD38 has emerged as a potential therapeutic target for patients with systemic lupus erythematosus (SLE) but it is not known whether CD38 alters CD4+ T cell function. Using primary human T cells and CD38-sufficient and -deficient Jurkat T cells, we demonstrate that CD38 shifts the T cell lipid profile of gangliosides from GM3 to GM2 by upregulating B4GALNT1 in a Sirtuin 1-dependent manner. Enhanced expression of GM2 causes ER stress by enhancing Ca2+ flux through the PLC_1-IP3 pathway. Interestingly, correction of the calcium overload by an IP3 receptor inhibitor, but not by a store-operated calcium entry (SOCE) inhibitor, improves IL-2 production by CD4+ T cells in SLE. This study demonstrates that CD38 affects calcium homeostasis in CD4+ T cells by controlling cell membrane lipid composition that results in suppressed IL-2 production. CD38 inhibition with biologics or small drugs should be expected to benefit patients with SLE.
Published in
CD38 in SLE CD4 T cells promotes Ca(2+) flux and suppresses interleukin-2 production by enhancing the expression of GM2 on the surface membrane
Katsuyama E, Humbel M, Suarez-Fueyo A et al. · Nature communications 2024 · PMID 39333474 · doi:10.1038/s41467-024-52617-7
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Also filed as BioProject PRJNA1139784 and SRA study SRP522077. Searching any of these in the dataset finder brings you back here.

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