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김희주Hee Joo Kim

가천대학교

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Exp. Mol. Med., May 01 2024, | https://doi.org/10.1038/s12276-024-01225-y TLR7-dependent eosinophil degranulation links psoriatic skin inflammation to small intestinal inflammatory changes in mice

Hee Joo Kim^1,2,11, Jinsun Jang^3,11, Kunhee Na³, Eun-Hui Lee⁴, Hyeon-Jung Gu³, Yoon Hee Lim⁴, Seul-A Joo⁵, Seung Eun Baek⁶, Joo-Young Roh^1,10, Han-Joo Maeng⁵, Yun Hak Kim^6,7, Young-Jae Lee^2,3,8, Byung-Chul Oh^2,3,9 and YunJae Jung^2,3,4

¹Department of Dermatology, Gachon Gil Medical Center, College of Medicine, Gachon University, Incheon 21565, Korea.

²Lee Gil Ya Cancer and Diabetes Institute, Gachon University, Incheon 21999, Korea.

³Department of Health Science and Technology, Gachon Advanced Institute for Health Science & Technology, Gachon University, Incheon 21999, Korea.

⁴Department of Microbiology, College of Medicine, Gachon University, Incheon 21999, Korea.

⁵College of Pharmacy, Gachon University, Incheon 21936, Korea.

⁶Department of Anatomy, School of Medicine, Pusan National University, Yangsan 50612, Korea.

⁷Department of Biomedical Informatics, School of Medicine, Pusan National University, Yangsan 50612, Korea.

⁸Department of Biochemistry, College of Medicine, Gachon University, Incheon 21999, Korea.

⁹Department of Physiology, College of Medicine, Gachon University, Incheon 21999, Korea.

¹⁰Present address: Department of Dermatology, Ewha Womans University Medical Center, College of Medicine, Ewha Womans University, Seoul 07804, Korea.

¹¹These authors contributed equally: Hee Joo Kim, Jinsun Jang.

Corresponding author : Correspondence to YunJae Jung.

Abstract

Recent evidence of gut microbiota dysbiosis in the context of psoriasis and the increased cooccurrence of inflammatory bowel disease and psoriasis suggest a close relationship between skin and gut immune responses. Using a mouse model of psoriasis induced by the Toll-like receptor (TLR) 7 ligand imiquimod, we found that psoriatic dermatitis was accompanied by inflammatory changes in the small intestine associated with eosinophil degranulation, which impaired intestinal barrier integrity. Inflammatory responses in the skin and small intestine were increased in mice prone to eosinophil degranulation. Caco-2 human intestinal epithelial cells were treated with media containing eosinophil granule proteins and exhibited signs of inflammation and damage. Imiquimod-induced skin and intestinal changes were attenuated in eosinophil-deficient mice, and this attenuation was counteracted by the transfer of eosinophils. Imiquimod levels and the distribution of eosinophils were positively correlated in the intestine. TLR7-deficient mice did not exhibit intestinal eosinophil degranulation but did exhibit attenuated inflammation in the skin and small intestine following imiquimod administration. These results suggest that TLR7-dependent bidirectional skin-to-gut communication occurs in psoriatic inflammation and that inflammatory changes in the intestine can accelerate psoriasis.

논문정보

형식Research article
게재일2024년 05월 (BRIC 등록일 2024-05-02)
연구진국내 연구진
분야 의약학 > 면역의학

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