{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,30]],"date-time":"2026-01-30T17:48:15Z","timestamp":1769795295025,"version":"3.49.0"},"reference-count":83,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2026,1,27]],"date-time":"2026-01-27T00:00:00Z","timestamp":1769472000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Ministerio de Ciencia e Innovaci\u00f3n (MCIN) \/ FEDER","award":["PID2021-122785OBI00"],"award-info":[{"award-number":["PID2021-122785OBI00"]}]},{"name":"Ministerio de Ciencia e Innovaci\u00f3n (MCIN) \/ FEDER","award":["PID2021-126820OB-I00"],"award-info":[{"award-number":["PID2021-126820OB-I00"]}]},{"DOI":"10.13039\/100008666","name":"Fundaci\u00f3 La Marat\u00f3 de 3Cat","doi-asserted-by":"publisher","award":["202005-30"],"award-info":[{"award-number":["202005-30"]}],"id":[{"id":"10.13039\/100008666","id-type":"DOI","asserted-by":"publisher"}]},{"name":"FPI-MCIN fellowship","award":["PRE2022-102424"],"award-info":[{"award-number":["PRE2022-102424"]}]},{"name":"FI-SDUR-2023 fellowship","award":["00036"],"award-info":[{"award-number":["00036"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Spinal muscular atrophy (SMA) is a neuromuscular disorder caused by loss of the SMN1 gene, reduced levels of SMN protein, and motor neuron degeneration. However, increasing evidence shows that SMA is a multisystemic disease with immune system involvement. We investigated how SMN deficiency affects lymphoid organ development and function using a severe SMA mouse model (SMN\u03947) and postmortem human fetal and postnatal tissues lacking SMN1 and carrying one or two SMN2 copies, consistent with type 0\u2013I SMA. Histology, immunostaining, and flow cytometry were used to examine tissue architecture and immune cell composition. SMN\u03947 mice displayed thymus, spleen, and bone marrow abnormalities, including mislocalization of T- and B-cells and expansion of resident macrophages. Bone marrow analysis revealed impaired B-cell development, suggesting intrinsic hematopoietic defects rather than apoptosis. Early treatment with a nusinersen-like antisense oligonucleotide, administered intracerebroventricularly or subcutaneously, restored SMN2 splicing, improved survival, motor function, and prevented lymphoid pathology. Human SMA samples exhibited similar, though milder, splenic alterations compared to SMN\u03947 mice, while thymic organization remained largely preserved. These findings demonstrate that SMN deficiency disrupts lymphoid organ development through defective bone marrow output and impaired immune cell maturation. Early SMN restoration prevents these abnormalities, highlighting immune dysfunction as a key component of SMA pathology.<\/jats:p>","DOI":"10.3390\/ijms27031274","type":"journal-article","created":{"date-parts":[[2026,1,27]],"date-time":"2026-01-27T15:41:56Z","timestamp":1769528516000},"page":"1274","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Lymphoid Organ Architecture and Hematopoiesis Disruption in Spinal Muscular Atrophy: Therapeutic Rescue by SMN Restoration"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0009-0009-9494-1584","authenticated-orcid":false,"given":"Paula","family":"Guillam\u00f3n","sequence":"first","affiliation":[{"name":"Experimental Neuromuscular Pathology Unit, Departament de Medicina Experimental, Facultat de Medicina, Universitat de Lleida, Av. Rovira Roure 80, 25198 Lleida, CAT, Spain"},{"name":"Institut de Recerca Biom\u00e8dica de Lleida\u2014Fundaci\u00f3 Dr. Pifarr\u00e9, IRBLleida, 25198 Lleida, CAT, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-7766-4846","authenticated-orcid":false,"given":"Georg","family":"Lindner","sequence":"additional","affiliation":[{"name":"Medicine Genetics Group, Vall d\u2019Hebron Research Institute (VHIR), Esfera UAB, 08035 Barcelona, CAT, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-2450-7732","authenticated-orcid":false,"given":"Joel","family":"Guillen","sequence":"additional","affiliation":[{"name":"Experimental Neuromuscular Pathology Unit, Departament de Medicina Experimental, Facultat de Medicina, Universitat de Lleida, Av. Rovira Roure 80, 25198 Lleida, CAT, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5153-1181","authenticated-orcid":false,"given":"Ala\u00f3","family":"Gatius","sequence":"additional","affiliation":[{"name":"Experimental Neuromuscular Pathology Unit, Departament de Medicina Experimental, Facultat de Medicina, Universitat de Lleida, Av. Rovira Roure 80, 25198 Lleida, CAT, Spain"},{"name":"Institut de Recerca Biom\u00e8dica de Lleida\u2014Fundaci\u00f3 Dr. Pifarr\u00e9, IRBLleida, 25198 Lleida, CAT, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"S\u00edlvia","family":"Gras","sequence":"additional","affiliation":[{"name":"Experimental Neuromuscular Pathology Unit, Departament de Medicina Experimental, Facultat de Medicina, Universitat de Lleida, Av. 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Rovira Roure 80, 25198 Lleida, CAT, Spain"},{"name":"Institut de Recerca Biom\u00e8dica de Lleida\u2014Fundaci\u00f3 Dr. Pifarr\u00e9, IRBLleida, 25198 Lleida, CAT, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ana\u00efs","family":"Panosa","sequence":"additional","affiliation":[{"name":"Institut de Recerca Biom\u00e8dica de Lleida\u2014Fundaci\u00f3 Dr. Pifarr\u00e9, IRBLleida, 25198 Lleida, CAT, Spain"},{"name":"Servei de Microsc\u00f2pia i Citometria, Universitat de Lleida, 25198 Lleida, CAT, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0802-7975","authenticated-orcid":false,"given":"Olga","family":"Tapia","sequence":"additional","affiliation":[{"name":"Department of Basic Medical Sciences, Institute of Biomedical Technologies (ITB), Universidad de La Laguna (ULL), 38200 Tenerife, CAN, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Conchi","family":"Mora","sequence":"additional","affiliation":[{"name":"Institut de Recerca Biom\u00e8dica de Lleida\u2014Fundaci\u00f3 Dr. Pifarr\u00e9, IRBLleida, 25198 Lleida, CAT, Spain"},{"name":"Research Group in Immunology and Metabolism (GRIM), Departament de Medicina Experimental, Facultat de Medicina, Universitat de Lleida, 25198 Lleida, CAT, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Josep E.","family":"Esquerda","sequence":"additional","affiliation":[{"name":"Institut de Recerca Biom\u00e8dica de Lleida\u2014Fundaci\u00f3 Dr. Pifarr\u00e9, IRBLleida, 25198 Lleida, CAT, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eduardo F.","family":"Tizzano","sequence":"additional","affiliation":[{"name":"Medicine Genetics Group, Vall d\u2019Hebron Research Institute (VHIR), Esfera UAB, 08035 Barcelona, CAT, Spain"},{"name":"Neuromuscular Pathology Unit, Fundaci\u00f3 Hospital Sant Joan de D\u00e9u, 08950 Esplugues de Llobregat, Barcelona, CAT, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7741-3223","authenticated-orcid":false,"given":"Olga","family":"Tarabal","sequence":"additional","affiliation":[{"name":"Experimental Neuromuscular Pathology Unit, Departament de Medicina Experimental, Facultat de Medicina, Universitat de Lleida, Av. Rovira Roure 80, 25198 Lleida, CAT, Spain"},{"name":"Institut de Recerca Biom\u00e8dica de Lleida\u2014Fundaci\u00f3 Dr. Pifarr\u00e9, IRBLleida, 25198 Lleida, CAT, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1972-0115","authenticated-orcid":false,"given":"Jordi","family":"Calder\u00f3","sequence":"additional","affiliation":[{"name":"Experimental Neuromuscular Pathology Unit, Departament de Medicina Experimental, Facultat de Medicina, Universitat de Lleida, Av. 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