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 β receptor 2 (TGF-βRII) 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.
Keywords: CD4(+) T cells; CP: Immunology; Th17; histone deacetylase 1; kidney function; systemic fungal infection.
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