BATF2 promotes HSC myeloid differentiation by amplifying IFN response mediators during chronic infection

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 duri...

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Veröffentlicht in:iScience 2023-02, Vol.26 (2), p.106059-106059, Article 106059
Hauptverfasser: Le, Duy T., Florez, Marcus A., Kus, Pawel, Tran, Brandon T., Kain, Bailee, Zhu, Yingmin, Christensen, Kurt, Jain, Antrix, Malovannaya, Anna, King, Katherine Y.
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Sprache:eng
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Zusammenfassung: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. [Display omitted] •The ATF-family transcription factor BATF2 is an amplifier of IFNγ responses in HSCs•BATF2 activates expression of the chemokine CCR5 to promote myeloid differentiation•Maraviroc therapy may prevent infection-associated cytopenias in chronic infection Biological sciences; Molecular physiology; Immunology
ISSN:2589-0042
2589-0042
DOI:10.1016/j.isci.2023.106059