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- Title
c-Myc-driven glycolysis polarizes functional regulatory B cells that trigger pathogenic inflammatory responses.
- Authors
Wang, Xu-Yan; Wei, Yuan; Hu, Bo; Liao, Yuan; Wang, Xiaodong; Wan, Wen-Hua; Huang, Chun-Xiang; Mahabati, Mahepali; Liu, Zheng-Yu; Qu, Jing-Rui; Chen, Xiao-Dan; Chen, Dong-Ping; Kuang, Dong-Ming; Wang, Xue-Hao; Chen, Yun
- Abstract
B cells secreting IL-10 functionally are recognized as functional regulatory B (Breg) cells; however, direct evidence concerning the phenotype, regulation, and functional and clinical relevance of IL-10-secreting Breg cells in humans is still lacking. Here, we demonstrate that, although IL-10 itself is anti-inflammatory, IL-10+ functional Breg cells in patients with systemic lupus erythematosus (SLE) display aggressive inflammatory features; these features shift their functions away from inducing CD8+ T cell tolerance and cause them to induce a pathogenic CD4+ T cell response. Functional Breg cells polarized by environmental factors (e.g., CPG-DNA) or directly isolated from patients with SLE mainly exhibit a CD24intCD27−CD38−CD69+/hi phenotype that is different from that of their precursors. Mechanistically, MAPK/ERK/P38-elicited sequential oncogenic c-Myc upregulation and enhanced glycolysis are necessary for the generation and functional maintenance of functional Breg cells. Consistently, strategies that abrogate the activity of ERK, P38, c-Myc, and/or cell glycolysis can efficiently eliminate the pathogenic effects triggered by functional Breg cells.
- Publication
Signal Transduction & Targeted Therapy, 2022, Vol 7, Issue 1, p1
- ISSN
2095-9907
- Publication type
Article
- DOI
10.1038/s41392-022-00948-6