The HDAC inhibitor panobinostat alleviates radiation-induced splenic B cell injury with concomitant transcriptomic changes in IL-17 signaling

Radiotherapy-induced B cell lymphopenia and hematopoietic suppression represent major complications of cancer therapy. The mechanisms that initiate B cell lineage regeneration from its source have yet to be elucidated, and targeted interventions are currently lacking. Here, we demonstrate that radiation exposure induces transcriptional dysregulation of histone deacetylases (HDACs) in splenic B cells. The pan-HDAC inhibitor panobinostat (PANO) specifically counteracts this radiation-induced immune injury. Building on this effect, PANO significantly restored hematopoietic progenitor cells (HPCs) in the bone marrow. In the spleen, it selectively reconstituted mature B cells and the follicular B cell (FoB) compartment without disrupting T cell homeostasis. This cellular specificity underscores PANO’s capacity to promote B cell regeneration across both central and peripheral compartments. Mechanistically, transcriptomic analysis revealed that PANO treatment was associated with the expression of genes in the IL-17 signaling pathway, as evidenced by upregulating critical mediators ( ACT1/Traf3ip2 , Traf5 , Traf6 ) and remodeling the chaperone network ( Stip1 , Dnaja1 , Hsp90 ). This coordinated enhancement of key B cell transcription factors ( Pax5 , Ebf1 , Myc ), coupled with suppression of pro-inflammatory mediators ( S100a8/a9 ), promoted B cell regeneration. Our study demonstrates that PANO enhances in situ proliferation of splenic mature B cells after radiation, accompanied by transcriptomic alterations in IL-17 signaling and HSP90 chaperone networks, providing hypothetical regulatory clues for B cell radioprotection.