AIM2 deficiency in CD4+ T cells promotes psoriasis-like inflammation by regulating Th17-Treg axis via AIM2-IKZF2 pathway.

Abstract

Psoriasis vulgaris remains a common inflammatory skin disease globally. The imbalance between Th17 and Treg cells plays an integral role in the pathogenesis of psoriasis vulgaris, but the underlying mechanisms remain obscure. The role of AIM2 in Treg cell function in psoriasis is unclear. We found that AIM2 expression is upregulated in peripheral blood and skin lesions from patients with psoriasis vulgaris when compared with healthy controls. In a psoriasis-like mouse model, CD4^creAim2^fl/fl mice showed aggravated psoriatic symptoms, increased Th17 cell and decreased Treg cell numbers in spleens and dLNs compared to Aim2^fl/fl mice. The loss of AIM2 in naïve CD4⁺ T cells promotes Th17 cell differentiation and decreases Treg cell numbers in vitro. Further, IKZF2 was identified as a downstream regulator of AIM2 through RNAseq analysis. AIM2 deficiency in CD4⁺ T cells downregulated IKZF2 mRNA expression. Silencing IKZF2 in naïve CD4⁺ T cells led to a significant increase in the expression of RORc and diminished FOXP3 expression. In summary, AIM2 may regulate the differentiation of Th17 and Treg cell by affecting IKZF2. Our findings might shed light on the pathogenesis of psoriasis and provide potential therapeutic targets for patients with psoriasis.