Title:

Mitochondrial DNA at the Heart of Inflammation and Autoimmunity

Abstract:
Mitochondrial stress releases oxidized mitochondrial DNA (Ox-mtDNA), a potent immune danger signal. We discovered that mitochondrial calcium-dependent permeability transition and VDAC oligomerization mediate the export of Ox-mtDNA fragments, which activate cytosolic NLRP3 inflammasome and cGAS-STING signaling to drive inflammation. While cell-intrinsic mtDNA sensing protects the host against infection and tissue injury, persistent Ox-mtDNA release into circulation promotes chronic inflammation and autoimmunity. Circulating Ox-mtDNA induces plasmacytoid dendritic cell-derived IL-1β and IL-21, driving T follicular helper (Tfh) cell activation, autoantibody production, and glomerulonephritis. These findings identify Ox-mtDNA as a key link between mitochondrial stress, inflammation and autoimmune pathology, providing new therapeutic insights.

About the speaker:

Hongxu Xian is an Associate Investigator at the Versiti Blood Research Institute and Assistant Professor of Biochemistry at the Medical College of Wisconsin. She received her Ph.D. from the National University of Singapore in 2019 and completed postdoctoral training with Dr. Michael Karin at UC San Diego in 2025. Xian’s research investigates how mitochondrial stress and oxidized mitochondrial DNA (Ox-mtDNA) regulate autoimmunity and aging. She is an Arthritis National Research Foundation Scholar and received awards from the American Association of Immunologists. Her lab seeks to translate mitochondrial signaling mechanisms into therapies for autoimmune disorders, neurodegenerative diseases, and cancer.

先红旭：威斯康星Versiti Blood Research Institute and Medical College of Wisconsin开始了自己的独立实验室。她的实验室致力于研究线粒体应激如何调控自身免疫性疾病、阿尔茨海默病和癌症中的细胞免疫学。Xian Lab将探讨mtDNA的免疫感应如何促进炎症和自身免疫。利用Versiti Blood Research Institute的优势， Xian Lab 将整合功能基因组学，蛋白质组学与细胞和分子免疫学技术, 与临床医生合作, 探究pDC、CD4 T细胞和小胶质细胞microglia之间的相互作用以及临床相关应用。

报告时间地点：

时间：2025/10/24 09:00-10:00

地点：#腾讯会议：399-374-353