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

Yue Xin; Ming Yang; Zhidan Zhao; Zhenghao He; Yang Mei; Feng Xiong; Fen Tan; Anqun Chen; Christopher Chang; Helong Dai; Haijing Wu; Qianjin Lu

doi:10.1016/j.jaut.2024.103351

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

J Autoimmun. 2024 Dec 16:150:103351. doi: 10.1016/j.jaut.2024.103351. Online ahead of print.

Authors

Yue Xin¹, Ming Yang¹, Zhidan Zhao¹, Zhenghao He², Yang Mei¹, Feng Xiong¹, Fen Tan¹, Anqun Chen³, Christopher Chang⁴, Helong Dai⁵, Haijing Wu⁶, Qianjin Lu⁷

Affiliations

¹ Department of Dermatology, the Second Xiangya Hospital, Central South University, Hunan Key Laboratory of Medical Epigenomics, Changsha, Hunan, China.
² Department of Plastic Surgery, Zhongshan City People's Hospital, Zhongshan, Guangdong, China.
³ Department of Nephrology, The Second Xiangya Hospital of Central South University, Changsha, Hunan, China; Hunan Key Laboratory of Kidney Disease and Blood Purification, Changsha, China.
⁴ Division of Immunology, Allergy and Pediatric Rheumatology, Joe DiMaggio Children's Hospital, Memorial Healthcare System, Hollywood, FL, 33021, USA.
⁵ Department of Kidney Transplantation, Center of Organ Transplantation, the Second Xiangya Hospital, Central South University, Changsha, Hunan, China. Electronic address: [email protected].
⁶ Department of Dermatology, the Second Xiangya Hospital, Central South University, Hunan Key Laboratory of Medical Epigenomics, Changsha, Hunan, China; The Furong Laboratory, Changsha, Hunan, China. Electronic address: [email protected].
⁷ Department of Dermatology, the Second Xiangya Hospital, Central South University, Hunan Key Laboratory of Medical Epigenomics, Changsha, Hunan, China; Institute of Dermatology, Chinese Academy of Medical Sciences and Peking Union Medical College, Nanjing, Jiangsu, China. Electronic address: [email protected].

PMID: 39689661
DOI: 10.1016/j.jaut.2024.103351

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.

Keywords: AIM2; IKZF2; Immune regulation; Psoriasis vulgaris; Th17; Treg.