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Alliance"],"published-print":{"date-parts":[[2023,9]]},"abstract":"<jats:p>Niemann\u2013Pick disease type C1 (NPC1) is a fatal lysosomal storage disorder characterized by progressive neuronal degeneration. Its key pathogenic events remain largely unknown. We have, herein, found that neonatal BM\u2013derived cell transplantation can ameliorate Purkinje cell degeneration in NPC1 mice. We subsequently addressed the impact of the peripheral immune system on the neuropathogenesis observed in NPC1 mice. The depletion of mature lymphocytes promoted NPC1 phenotypes, thereby suggesting a neuroprotective effect of lymphocytes. Moreover, the peripheral infusion of CD4-positive cells (specifically, of regulatory T cells) from normal healthy donor ameliorated the cerebellar ataxic phenotype and enhanced the survival of Purkinje cells. Conversely, the depletion of regulatory T cells enhanced the onset of the neurological phenotype. On the other hand, circulating inflammatory monocytes were found to be involved in the progression of Purkinje cell degeneration, whereas the depletion of resident microglia had little effect. Our findings reveal a novel role of the adaptive and the innate immune systems in NPC1 neuropathology.<\/jats:p>","DOI":"10.26508\/lsa.202201881","type":"journal-article","created":{"date-parts":[[2023,6,27]],"date-time":"2023-06-27T14:25:11Z","timestamp":1687875911000},"page":"e202201881","update-policy":"https:\/\/doi.org\/10.26508\/lsa.crossmarkpolicy","source":"Crossref","is-referenced-by-count":4,"title":["Peripheral immune system modulates Purkinje cell degeneration in Niemann\u2013Pick disease type C1"],"prefix":"10.26508","volume":"6","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2273-6700","authenticated-orcid":true,"given":"Toru","family":"Yasuda","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/03fvwxc59","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Human Genetics, National Center for Child Health and Development","place":[", Tokyo, 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