Histone demethylase JARID1C/KDM5C regulates Th17 cells by increasing IL-6 expression in diabetic plasmacytoid dendritic cells

• DOI: 10.1172/jci.insight.172959
• Publication Date: 2024-06-23T18:00:36Z
• Authors: Christopher O. Audu; Sonya J. Wolf; Amrita D. Joshi; Jadie Y. Moon; William J. Melvin; Sriganesh B. Sharma; Frank M. Davis; Andrea T. Obi; Rachel Wasikowski; Lam C. Tsoi; Emily C. Barrett; Kevin D. Mangum; Tyler M. Bauer; Steven L. Kunkel; Beth B. Moore; Katherine A. Gall...
• Keywords: Demethylase; Interleukin-23

Plasmacytoid dendritic cells (pDCs) are first responders to tissue injury, where they prime naive T cells. The role of pDCs in physiologic wound repair has been examined, but little is known about diabetic and their interactions with CD4+ Diabetic wounds characterized by increased levels inflammatory IL-17A cytokine, partly due Th17 This excess, impairs repair. Here, using human murine healing models, we found that produced excess IL-6 TGF-β these cytokines skewed toward a phenotype following cutaneous injury. Further, identified cytokine production regulated histone demethylase, Jumonji AT-rich interactive domain 1C demethylase (JARID1C). Decreased JARID1C transcription pDCs, this process was upstream an IFN-I/TYK2/JAK1,3 signaling pathway. When inhibited nondiabetic production. Together, suggests epigenetically altered increase expression then affects cell phenotype. These findings identify therapeutically manipulable pathway wounds.