In conclusion, our data demonstrate that TCF4 negatively regulates IL-17C and ZC3H12A expression in human KCs and in a mouse model of dermatitis, and that IL-17C promotes the expression of ZC3H12A and NFKBIZ in an IL-17RA/RE–dependent manner and together work collectively to promote inflammation that becomes self-sustaining. Here, ZC3H12A is linked to dry eye syndrome.