Katsuyama, TakayukiJuárez Martín-Delgado, IgnacioKrishfield, Suzanne MKyttaris, Vasileios CMoulton, Vaishali R2024-01-312024-01-312020-03-24Katsuyama T, Martin-Delgado IJ, Krishfield SM, Kyttaris VC, Moulton VR. Splicing factor SRSF1 controls T cell homeostasis and its decreased levels are linked to lymphopenia in systemic lupus erythematosus. Rheumatology (Oxford). 2020 Aug 1;59(8):2146-2155. doi: 10.1093/rheumatology/keaa0941462-03241462-033210.1093/rheumatology/keaa094https://hdl.handle.net/20.500.14352/96996Objective: Lymphopenia is a frequent clinical manifestation and risk factor for infections in SLE, but the underlying mechanisms are not fully understood. We previously identified novel roles for the RNA-binding protein serine arginine-rich splicing factor 1 (SRSF1) in the control of genes involved in signalling and cytokine production in human T cells. SRSF1 is decreased in T cells from patients with SLE and associates with severe disease. Because SRSF1 controls the expression of apoptosis-related genes, we hypothesized that SRSF1 controls T cell homeostasis and, when reduced, leads to lymphopenia. Methods: We evaluated SRSF1 expression in T cells from SLE patients by immunoblots and analysed its correlation with clinical parameters. T cell conditional Srsf1 knockout mice were used to evaluate lymphoid cells and apoptosis by flow cytometry. Quantitative PCR and immunoblots were used to assess Bcl-xL mRNA and protein expression. SRSF1 overexpression was performed by transient transfections by electroporation. Results: We found that low SRSF1 levels correlated with lymphopenia in SLE patients. Selective deletion of Srsf1 in T cells in mice led to T cell lymphopenia, with increased apoptosis and decreased expression of the anti-apoptotic Bcl-xL. Lower SRSF1 expression correlated with low Bcl-xL levels in T cells and lower Bcl-xL levels associated with lymphopenia in SLE patients. Importantly, overexpression of SRSF1 rescued survival of T cells from patients with SLE. Conclusion: Our studies uncovered a previously unrecognized role for SRSF1 in the control of T cell homeostasis and its reduced expression as a molecular defect that contributes to lymphopenia in systemic autoimmunity.engAttribution-NonCommercial-NoDerivatives 4.0 Internationalhttp://creativecommons.org/licenses/by-nc-nd/4.0/journal articlehttps://academic.oup.com/rheumatology/article/59/8/2146/581112332206811https://pubmed.ncbi.nlm.nih.gov/32206811/open access612.017Bcl-xLSRSF1T cellsHomeostasisLymphopeniaSystemic lupus erythematosusInmunología2412 Inmunología