{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T14:34:54Z","timestamp":1786977294062,"version":"build-2736575974"},"reference-count":44,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2024,2,12]],"date-time":"2024-02-12T00:00:00Z","timestamp":1707696000000},"content-version":"vor","delay-in-days":11,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Brain and Behavior"],"published-print":{"date-parts":[[2024,2]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>Vitamin D deficiency is a risk factor for Parkinson's disease (PD) and vitamin D supplementation robustly alleviates neurodegeneration in PD models. However, the mechanisms underlying this effect require further clarification. Current evidence suggests that harnessing regulatory T cells (Treg) may mitigate neuronal degeneration. In this study, we investigated the therapeutic effects of vitamin D receptor activation by calcitriol on PD, specifically focusing on its role in Treg.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Hemiparkinsonian mice model was established through the injection of 6\u2010OHDA into the striatum. Mice were pretreated with calcitriol before 6\u2010OHDA injection. The motor performance, dopaminergic neuronal survival, contents of dopamine, and dopamine metabolites were evaluated. The pro\u2010inflammatory cytokines levels, T\u2010cell infiltration, mRNA expression of indicated microglial M1\/M2 phenotypic markers, and microglial marker in the midbrain were detected. Populations of Treg in the splenic tissues were assessed using a flow cytometry assay. PC61 monoclonal antibody was applied to deplete Treg in vivo.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>We show that calcitriol supplementation notably improved motor performance and reduced dopaminergic degeneration in the 6\u2010OHDA\u2010induced PD model. Mechanistically, calcitriol promoted anti\u2010inflammatory\/neuroprotective Treg and inhibited pro\u2010inflammatory\/neurodestructive effector T\u2010cell generation in this model. This process significantly inhibited T\u2010cell infiltration in the midbrain, restrained microglial activation, microglial M1 polarization, and decreased pro\u2010inflammatory cytokines release. This more favorable inflammatory microenvironment rescued dopaminergic degeneration. To further verify that the anti\u2010inflammatory effects of calcitriol are associated with Treg expansion, we applied an antibody\u2010mediated Treg depletion assay. As predicted, the anti\u2010inflammatory effects of calcitriol in the PD model were diminished following Treg depletion.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>These findings suggest that calcitriol's anti\u2010inflammatory and neuroprotective effects in PD are associated with its potential to boost Treg expansion.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/brb3.3373","type":"journal-article","created":{"date-parts":[[2024,2,12]],"date-time":"2024-02-12T20:13:58Z","timestamp":1707768838000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Calcitriol restrains microglial M1 polarization and alleviates dopaminergic degeneration in hemiparkinsonian mice by boosting regulatory T\u2010cell expansion"],"prefix":"10.1002","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2248-9719","authenticated-orcid":false,"given":"Yangzhi","family":"Xie","sequence":"first","affiliation":[{"name":"Department of Neurology, The Affiliated Nanhua Hospital, Hengyang Medical School University of South China  Hengyang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liang","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Neurology, The Affiliated Nanhua Hospital, Hengyang Medical School University of South China  Hengyang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiacheng","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Intensive Care Unit, The Affiliated Nanhua Hospital, Hengyang Medical School University of South China  Hengyang 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