최용호 (경상국립대학교, University of Minnesota) | 한빛사논문 > 한빛사

한빛사논문

조회433

경상국립대학교, University of Minnesota

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J. Autoimmun., May 23 2024, 147 S0896-8411(24)00090-8 | https://doi.org/10.1016/j.jaut.2024.103256 The autoimmune response induced by α-synuclein peptides drives neuronal cell death and glial cell activation

Yong-ho Choe ^a,b,c,1, Min Gi Jo ^d,e,1, Bo Gyu Kim^a,f, Sangwon Lee ^a,f, Bina Lee ^e, Seon-Hee Kim ^e, Hyemin Seong ^e,g, Woong-Sun Yoo ^g, Minkyeong Kim ^h, Dong-Kun Lee^f,i, Seong Jae Kim ^g, Seung Pil Yun ^e,f, Mingyo Kim^a,f,j

^aDivision of Rheumatology. Department of Internal Medicine, Gyeongsang National University Hospital, Jinju 52727, Republic of Korea

^bLillehei Heart Institute and Cardiovascular Division, Department of Medicine, University of Minnesota, Minneapolis 55414, MN, United States

^cDepartment of Theriogenology and Biotechnology, College of Veterinary Medicine, Gyeongsang National University, Jinju 52828, Republic of Korea

^dDepartment of Pathology, College of Medicine, Kyung Hee University, Seoul 02447, Republic of Korea

^eDepartment of Pharmacology, Institute of Medical Science, College of Medicine, Gyeongsang National University, Jinju 52727, Republic of Korea

^fDepartment of Convergence Medical Science, College of Medicine, Gyeongsang National University, Jinju 52727, Republic of Korea

^gDepartment of Ophthalmology, Institute of Medical Science, College of Medicine, Gyeongsang National University, Jinju 52727, Republic of Korea

^hDepartment of Neurology, Gyeongsang National University Hospital, Jinju 52727, Republic of Korea

ⁱDepartment of Physiology, Institute of Medical Science, College of Medicine, Gyeongsang National University, Jinju 52727, Republic of Korea

^jDepartment of Internal Medicine, College of Medicine, Gyeongsang National University Hospital, Jinju 52727, Republic of Korea

¹These authors contributed equally.

Corresponding authors: Seung Pil Yun, Mingyo Kim

Abstract

Parkinson's disease (PD) is a progressive neurodegenerative disorder associated with the loss of dopaminergic neurons and neuroinflammation. Recent studies have identified a role of T cells in the pathogenesis of PD. Additionally, these studies suggested that α-synuclein (α-Syn) is related to abnormal T-cell responses and may act as an epitope and trigger autoimmune T-cell responses. However, it is unclear whether the α-Syn-mediated autoimmune response occurs and whether it is related to neuronal cell death and glial cell activation. In this study, we investigated the autoimmune T-cell response induced by α-Syn peptides and evaluated the neurotoxic effect of the α-Syn peptide-mediated autoimmune response. The immunization of mice with α-Syn peptides resulted in enhanced autoimmune responses, such as the peptide recall response, polarization toward Th1/Th17 cells, and regulatory T cell imbalance. Furthermore, the α-Syn autoimmune response led to the death of primary neurons cocultured with splenocytes. Treatment with conditioned media from α-Syn peptide-immunized splenocytes induced microglia and toxic A1-type astrocyte activation. Taken together, our results provide evidence of the potential role of the α-Syn-initiated autoimmune response and its contribution to neuronal cell death and glial cell activation.

논문정보

형식Research article
게재일2024년 05월 (BRIC 등록일 2024-05-27)
연구진국내(교신)+국외 연구진
분야 생명과학 > 면역학

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