Publication Date
2-17-2023
Journal
iScience
DOI
10.1016/j.isci.2023.106059
PMID
36824275
PMCID
PMC9942003
PubMedCentral® Posted Date
1-27-2023
PubMedCentral® Full Text Version
Post-print
Published Open-Access
yes
Keywords
Biological sciences, Molecular physiology, Immunology
Abstract
Basic leucine zipper ATF-like transcription factor 2 (BATF2), an interferon-activated immune response regulator, is a key factor responsible for myeloid differentiation and depletion of HSC during chronic infection. To delineate the mechanism of BATF2 function in HSCs, we assessed Batf2 KO mice during chronic infection and found that they produced less pro-inflammatory cytokines, less immune cell recruitment to the spleen, and impaired myeloid differentiation with better preservation of HSC capacity compared to WT. Co-IP analysis revealed that BATF2 forms a complex with JUN to amplify pro-inflammatory signaling pathways including CCL5 during infection. Blockade of CCL5 receptors phenocopied Batf2 KO differentiation defects, whereas treatment with recombinant CCL5 was sufficient to rescue IFNγ-induced myeloid differentiation and recruit more immune cells to the spleen in Batf2 KO mice. By revealing the mechanism of BATF2-induced myeloid differentiation of HSCs, these studies elucidate potential therapeutic strategies to boost immunity while preserving HSC function during chronic infection.
Graphical Abstract
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Biochemistry, Biophysics, and Structural Biology Commons, Biology Commons, Medical Immunology Commons, Medical Molecular Biology Commons, Medical Specialties Commons
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