TLR7-dependent eosinophil degranulation links psoriatic skin inflammation to small intestinal inflammatory changes in mice

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. © The Author(s) 2024.; Psoriasis is a long-lasting skin disease that involves the body’s immunee system. However, it’s not clear how the immune responses in the skin and gut are connected to psoriasis. In this research, scientists discovered that skin inflammation due to psoriasis in mice causes changes in the small intestine, mainly impacting the immune environment. The research also showed that psoriasis was less severe in mice without eosinophils, a kind of white blood cell. The scientists concluded that there’s a two-way interaction between the skin and the gut in psoriasis, and that the unique immune characteristics of the small intestine are crucial in psoriasis development. This study could possibly lead to new psoriasis treatments. This summary was initially drafted using artificial intelligence, then revised and fact-checked by the author. © The Author(s) 2024.