2026-08-20T15:35:06Zhttps://docta.ucm.es/rest/oai/request

oai:docta.ucm.es:20.500.14352/1072112025-03-18T15:37:53Zcom_20.500.14352_14col_20.500.14352_15

Marín Marín, Ana Victoria Jiménez Reinoso, Anaïs Mazariegos, Marina S. Román Ortiz, Elena Regueiro González-Barros, José Ramón 2024-07-30T08:57:52Z 2024-07-30T08:57:52Z 2022-10-18 Marin AV, Jiménez-Reinoso A, Mazariegos MS, Román-Ortiz E and Regueiro JR (2022) T-cell receptor signaling in Schimke immuno-osseous dysplasia is SMARCAL1-independent. Front. Immunol. 13:979722. doi: 10.3389/fimmu.2022.979722 10.3389/fimmu.2022.979722 https://hdl.handle.net/20.500.14352/107211 1664-3224 https://doi.org/10.3389/fimmu.2022.979722 https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2022.979722/full Schimke immuno-osseous dysplasia (SIOD) caused by mutations in SMARCAL1 is an ultra-rare disease characterized by specific facial features, skeletal dysplasia, and steroid-resistant nephrotic syndrome, which often leads to kidney failure and requires transplantation. Cellular (T-cell) deficiency, lymphopenia, and infections have been frequently reported, but whether they are due to T-cell-intrinsic defects in T-cell receptor (TCR) signaling associated with SMARCAL1 deficiency or to T-cell-extrinsic effects such as the impaired proliferation of hematopoietic precursors or T-cell-specific immunosuppression after renal transplantation remains unknown. We have explored the effects of SMARCAL1 deficiency on T-cell receptor signaling in primary and immortalized T cells from a 9-year-old SIOD patient under immunosuppression treatment when compared to healthy donors. Immortalized T cells recapitulated the SMARCAL1 deficiency of the patient, as judged by their impaired response to gamma irradiation. The results indicated that TCR-mediated signaling was normal in SIOD-derived immortalized T cells but strongly impaired in the primary T cells of the patient, although rescued with TCR-independent stimuli such as PMA + ionomycin, suggesting that SIOD-associated T-cell signaling is not intrinsically defective but rather the result of the impaired proliferation of hematopoietic precursors or of T-cell-specific immunosuppression. The lack of early thymic emigrants in our patients may support the former hypothesis. eng http://creativecommons.org/licenses/by/4.0/ open access Attribution 4.0 International T-cell receptor signaling in Schimke immunoosseous dysplasia is SMARCAL1-independent journal article