Mitochondria Activity and CXCR4Collaboratively Promote the Differentiation of CD11c + B Cells Induced by TLR9 in Lupus
- Author:
Sung Hoon JANG
1
;
Joo Sung SHIM
;
Jieun KIM
;
Eun Gyeol SHIN
;
Jong Hwi YOON
;
Lucy Eunju LEE
;
Ho-Keun KWON
;
Jason Jungsik SONG
Author Information
- Publication Type:Brief Communication
- From:Immune Network 2024;24(4):e25-
- CountryRepublic of Korea
- Language:English
- Abstract: Lupus is characterized by the autoantibodies against nuclear Ags, underscoring the importance of identifying the B cell subsets driving autoimmunity. Our research focused on the mitochondrial activity and CXCR4 expression in CD11c + B cells from lupus patients after ex vivo stimulation with a TLR9 agonist, CpG-oligodeoxyribonucleotide (ODN). We also evaluated the response of CD11c + B cells in ODN-injected mice. Post-ex vivo ODN stimulation, we observed an increase in the proportion of CD11chi cells, with elevated mitochondrial activity and CXCR4 expression in CD11c + B cells from lupus patients. In vivo experiments showed similar patterns, with TLR9 stimulation enhancing mitochondrial and CXCR4 activities in CD11chi B cells, leading to the generation of anti-dsDNA plasmablasts. The CXCR4 inhibitor AMD3100 and the mitochondrial complex I inhibitor IM156 significantly reduced the proportion of CD11c + B cells and autoreactive plasmablasts. These results underscore the pivotal roles of mitochondria and CXCR4 in the production of autoreactive plasmablasts.
