Oxidative phosphorylation regulates B cell effector cytokines and promotes inflammation in multiple sclerosis.
|
| Abstract |
Dysregulated B cell cytokine production contributes to pathogenesis of immune-mediated diseases including multiple sclerosis (MS); however, the underlying mechanisms are poorly understood. In this study we investigated how cytokine secretion by pro-inflammatory (GM-CSF-expressing) and anti-inflammatory (IL-10-expressing) B cells is regulated. Pro-inflammatory human B cells required increased oxidative phosphorylation (OXPHOS) compared with anti-inflammatory B cells. OXPHOS reciprocally modulated pro- and anti-inflammatory B cell cytokines through regulation of adenosine triphosphate (ATP) signaling. Partial inhibition of OXPHOS or ATP-signaling including with BTK inhibition resulted in an anti-inflammatory B cell cytokine shift, reversed the B cell cytokine imbalance in patients with MS, and ameliorated neuroinflammation in a myelin oligodendrocyte glycoprotein (MOG)-induced experimental autoimmune encephalitis mouse model. Our study identifies how pro- and anti-inflammatory cytokines are metabolically regulated in B cells and identifies ATP and its metabolites as a "fourth signal" that shapes B cell responses and is a potential target for restoring the B cell cytokine balance in autoimmune diseases.
|
|---|---|
| Authors | Rui Li, Yanting Lei, Ayman Rezk, Diego A Espinoza, Jing Wang, Huiru Feng, Bo Zhang, Isabella P Barcelos, Hang Zhang, Jing Yu, Xinrui Huo, Fangyi Zhu, Changxin Yang, Hao Tang, Amy C Goldstein, Brenda L Banwell, Hakon Hakonarson, Hongwei Xu, Michael Mingueneau, Bo Sun, Hulun Li, Amit Bar-Or |
| Journal | Science immunology (Sci Immunol) Vol. 9 Issue 95 Pg. eadk0865 (May 03 2024) ISSN: 2470-9468 [Electronic] United States |
| PMID | 38701189 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't) |
| Chemical References |
|
| Topics |
|
Join CureHunter, for free Research Interface BASIC access!
Realize the full power of the drug-disease research graph!