c-Myc-driven glycolysis polarizes functional regulatory B cells that trigger pathogenic inflammatory responses.
Signal Transduct Target Ther
; 7(1): 105, 2022 04 18.
Article
in En
| MEDLINE
| ID: mdl-35430810
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.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
B-Lymphocytes, Regulatory
/
Lupus Erythematosus, Systemic
Limits:
Humans
Language:
En
Journal:
Signal Transduct Target Ther
Year:
2022
Document type:
Article
Affiliation country:
China