LAG3 limits regulatory T cell proliferation in α-synuclein gut-to-brain transmission model
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Le résumé fourni par la source
BACKGROUND: Pathological α-synuclein (α-syn) can spread from the gut to the central nervous system (CNS), with CD4 + T cells playing a key role in this process. Lymphocyte activation gene 3 (LAG3) is involved in intestinal inflammation, regulates CD4 + T cell proliferation and function, and can specifically bind to pathological α-syn during cell-to-cell transmission. However, it remains unclear whether LAG3 is involved in the spread of pathological α-syn from the gut to the brain. METHODS: We utilized LAG3 knockout mice, combined with injection of α-syn preformed fibril (PFF) into the longitudinal and intermediate muscle layers of the pylorus and duodenum to model Parkinson's disease (PD). We used Immunohistochemistry staining, Western Blot, Flow cytometry to detect the changes of TH, α-syn, pro-inflammatory factors, barrier-related proteins and CD4 + T cells differentiation. RESULTS: Our results show that LAG3 knockout partially alleviates psychological and behavioral deficits, dopamine system damage, and the gut-to-brain transmission of α-syn, which correlates with enhanced regulatory T cell (Treg) cell proliferation. Furthermore, LAG3 knockout improved intestinal dysfunction and increased the expression of tight junction proteins in both the gut and the blood-brain barrier (BBB). In CD4 + T cells isolated from the spleen, LAG3 knockout suppressed the aggregation of α-syn PFF, thereby inhibiting the toxic T-cell response induced by α-syn PFF. LAG3 deficiency also enhanced the IL-2/STAT5 signaling pathway, which regulates Treg proportions both in vivo and in vitro. CONCLUSIONS: Our findings demonstrated that LAG3 intrinsically limits Treg cell proliferation and function in the environment with pathological α-syn and promotes the gut-to-brain transmission of α-syn.
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Le contrôle bibliographique ouvert
DOI retrouvé dans Crossref DOI retrouvé ; titre concordant.
- Titre Crossref
- LAG3 limits regulatory T cell proliferation in α-synuclein gut-to-brain transmission model
- Date Crossref
- 05/07/2025
- Éditeur
- Springer Science and Business Media LLC
- Type
- journal-article
Ce recoupement confirme des métadonnées liées au DOI. Il ne confirme ni la méthode ni les conclusions de l’étude, et il ne compte pas comme une seconde source scientifique indépendante.
Où se fait cette recherche
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First Affiliated Hospital of Guangzhou Medical University Department of Neurology pays non établi dans la noticeÉtablissement de santé
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Guangzhou Medical University pays non établi dans la noticeUniversité ou école supérieure
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Xinjiang Medical University Department of Neurology pays non établi dans la noticeUniversité ou école supérieure
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Second Affiliated Hospital of Xinjiang Medical University pays non établi dans la noticeUniversité ou école supérieure
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Hong Kong Polytechnic University Key Laboratory of Food Biological Safety Control pays non établi dans la noticeUniversité ou école supérieure
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Shenzhen Polytechnic University pays non établi dans la noticeUniversité ou école supérieure
Department of Neurology — First Affiliated Hospital of Guangzhou Medical University, Guangzhou Medical University et Department of Neurology — Xinjiang Medical University, avec 3 autres affiliations.
Une affiliation ne permet pas de déduire la nationalité d’un auteur.