| First Author | Penninger P | Year | 2024 |
| Journal | Cell Rep | Volume | 43 |
| Issue | 12 | Pages | 114993 |
| PubMed ID | 39580799 | Mgi Jnum | J:360815 |
| Mgi Id | MGI:7852082 | Doi | 10.1016/j.celrep.2024.114993 |
| Citation | Penninger P, et al. (2024) HDAC1 fine-tunes Th17 polarization in vivo to restrain tissue damage in fungal infections. Cell Rep 43(12):114993 |
| abstractText | Histone deacetylases (HDACs) contribute to shaping many aspects of T cell lineage functions in anti-infective surveillance; however, their role in fungus-specific immune responses remains poorly understood. Using a T cell-specific deletion of HDAC1, we uncover its critical role in limiting polarization toward Th17 by restricting expression of the cytokine receptors gp130 and transforming growth factor beta receptor 2 (TGF-betaRII) in a fungus-specific manner, thus limiting Stat3 and Smad2/3 signaling. Controlled release of interleukin-17A (IL-17A) and granulocyte-macrophage colony-stimulating factor (GM-CSF) is vital to minimize apoptotic processes in renal tubular epithelial cells in vitro and in vivo. Consequently, animals harboring excess Th17-polarized HDCA1-deficient CD4(+) T cells develop increased kidney pathology upon invasive Candida albicans infection. Importantly, pharmacological inhibition of class I HDACs similarly increased IL-17A release by both mouse and human CD4(+) T cells. Collectively, this work shows that HDAC1 controls T cell polarization, thus playing a critical role in the antifungal immune defense and infection outcomes. |
