Interleukin-9 blockage reduces early hepatic granuloma formation and fibrosis during Schistosoma japonicum infection in mice

Immunology. 2019 Dec;158(4):296-303. doi: 10.1111/imm.13111. Epub 2019 Sep 17.

Abstract

Hepatic fibrosis induced by schistosomes is regulated by a complex network of cytokines. T helper type 9 (Th9) cells are a new type of effector T helper cells, which mainly secrete the specific cytokine interleukin-9 (IL-9). Interleukin-9 has been shown to contribute to liver fibrosis in patients with chronic hepatitis B and in a mouse model due to carbon tetrachloride. However, the role of IL-9 in schistosomiasis fibrosis remains unknown. In this study, we investigated the roles of IL-9 in schistosomiasis through in vivo and in vitro studies. The in vivo studies found that neutralization of IL-9 reduced liver granulomatous inflammation and collagen deposition around parasite eggs. The in vitro studies found that the treatment of primary hepatic stellate cells with IL-9 induced a significant increase of collagen and α-smooth-muscle actin. Moreover, we also described the dynamics and relevance of IL-9 and IL-4 in mice infected with Schistosoma japonicum. We found that IL-9 might appear more quickly and at higher levels than IL-4. Hence, our findings indicated that IL-9 might play a role in regulating hepatic fibrosis in early-stage schistosomiasis and become a promising approach for regulating hepatic fibrosis caused by S. japonicum.

Keywords: egg granuloma; hepatic fibrosis; interleukin-9; schistosomiasis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cells, Cultured
  • Collagen / metabolism
  • Disease Models, Animal
  • Female
  • Fibrosis
  • Granuloma / immunology
  • Granuloma / therapy*
  • Humans
  • Inflammation / immunology
  • Inflammation / therapy*
  • Interleukin-4 / metabolism
  • Interleukin-9 / antagonists & inhibitors
  • Interleukin-9 / metabolism*
  • Liver Diseases / immunology
  • Liver Diseases / therapy*
  • Mice
  • Mice, Inbred Strains
  • Parasite Egg Count
  • Schistosoma japonicum / physiology*
  • Schistosomiasis japonica / immunology
  • Schistosomiasis japonica / therapy*
  • T-Lymphocytes, Helper-Inducer / immunology*

Substances

  • Interleukin-9
  • Interleukin-4
  • Collagen