Contribution of tissue transglutaminase to the severity of hepatic fibrosis resulting from Schistosoma japonicum infection through the regulation of IL-33/ST2 expression

Zhi-Yong Li (1) , Linzhuo Xiao (1) , Guiying Lin (1) , Juanjuan Tang (1) , Yuqiang Chen (1) , Lan Chen (1) , Baoqi Li (1) , Meiling Wu (1) , Shuyan Liu (1) , Chuqin Huang (1) , Dominique Ferrandon (2, 1) , Zi Li (1)

1 Guangzhou Medical University
2 M3I - Modèles Insectes de l'Immunité Innée

Background: Tissue transglutaminase (tTG)-regulating IL-13 plays an important role in the pathogenesis of liver fibrosis resulting from Schistosoma japonicum (Sj) infection. IL-33 and its receptor ST2 are involved in Th2-biased immune responses through the release of IL-5 and IL-13 and subsequent hepatic granuloma pathology induced by Sj infection. However, the relationship between tTG, IL-33/ST2, and liver fibrosis during Schistosoma infection has not been established. Results: This study investigated the link between tTG and IL-33/ST2 in the induction of liver fibrogenesis during Sj infection in mice. The extent of liver fibrosis coincided with an increase in tTG and IL-33/ST2 expression in the liver of infected mice between five to eight weeks, with a peak of correlation at six weeks after Sj infection. The inhibition of tTG activity through cystamine administration or gene knockout alleviated the level of TLR4, NF-κB pathway molecules, IL-33/ST2, and the severity of liver fibrosis resulting from Sj infection. Conclusions: These results indicate that during Sj infection tTG may control liver fibrosis at least partially through TLR4, NF-κB pathway activation and then IL-33/ST2. tTG, IL-33 or ST2 might be promising drug targets against liver fibrosis induced by Sj infection.

Mots clés: Tissue transglutaminase; IL-33; ST2; Liver fbrosis; Schistosoma japonicum

Domaines: Maladies infectieuses; Hépatologie et Gastroentérologie; Immunité innée; Parasitologie

Zhi-Yong Li, Linzhuo Xiao, Guiying Lin, Juanjuan Tang, Yuqiang Chen, et al.. Contribution of tissue transglutaminase to the severity of hepatic fibrosis resulting from Schistosoma japonicum infection through the regulation of IL-33/ST2 expression. Parasites & Vectors, 2019, 12, pp.302. ⟨10.1186/s13071-019-3542-4⟩. ⟨hal-02354571⟩