Fig. 6: Schematic of IL-17A-mediated JMJD3 regulation of keratinocyte functions in normal and diabetic wound keratinocytes.

(Top) In normal wounds, keratinocytes receive balanced environmental cues that support regulated JMJD3 activity, allowing appropriate H3K27me3 demethylation and expression of pro-migratory and inflammatory genes, promoting keratinocyte migration and timely recruitment of reparative immune cells. (Bottom) In diabetic wounds, elevated IL-17A engages the IL-17 receptor and signals through the TRAF6/NFκB pathway to drive increased JMJD3 expression, resulting in excessive H3K27me3 demethylation and increased expression of Itga3, Timp1, Ccl20, Cxcl1, Cxcl3, and Cxcl5. This cascade contributes to decreased keratinocyte migration, increased inflammatory immune cell recruitment, and impaired diabetic wound healing.