1. Academic Validation
  2. Butyrate induces STAT3/HIF-1α/IL-22 signaling via GPCR and HDAC3 inhibition to activate autophagy in head kidney macrophages from turbot (Scophthalmus maximus L.)

Butyrate induces STAT3/HIF-1α/IL-22 signaling via GPCR and HDAC3 inhibition to activate autophagy in head kidney macrophages from turbot (Scophthalmus maximus L.)

  • Fish Shellfish Immunol. 2023 Nov 15:143:109214. doi: 10.1016/j.fsi.2023.109214.
Jinjin Zhang 1 Wentao Wang 1 Shufei Liang 1 Xueqi Zhou 1 Rokeya Sultana Rekha 2 Gudmundur H Gudmundsson 3 Peter Bergman 2 Qinghui Ai 1 Kangsen Mai 1 Min Wan 4
Affiliations

Affiliations

  • 1 Key Laboratory of Aquaculture Nutrition and Feed, Ministry of Agriculture & Key Laboratory of Mariculture, Ministry of Education, College of Fisheries, Ocean University of China, Qingdao, China.
  • 2 Department of Laboratory Medicine, Karolinska Institutet, Stockholm, Sweden; The Immunodeficiency Unit, Infectious Disease Clinic, Karolinska University Hospital, Stockholm, Sweden.
  • 3 Department of Laboratory Medicine, Karolinska Institutet, Stockholm, Sweden; Biomedical Center, University of Iceland, Reykjavik, Iceland.
  • 4 Key Laboratory of Aquaculture Nutrition and Feed, Ministry of Agriculture & Key Laboratory of Mariculture, Ministry of Education, College of Fisheries, Ocean University of China, Qingdao, China. Electronic address: wanmin@ouc.edu.cn.
Abstract

As one of short-chain fatty acids, butyrate is an important metabolite of dietary fiber by the fermentation of gut commensals. Our recent study uncovered that butyrate promoted IL-22 production in fish macrophages to augment the host defense. In the current study, we further explored the underlying signaling pathways in butyrate-induced IL-22 production in fish macrophages. Our results showed that butyrate augmented the IL-22 expression in head kidney macrophages (HKMs) of turbot through binding to G-protein receptor 41 (GPR41) and GPR43. Moreover, histone deacetylase 3 (HDAC3) inhibition apparently up-regulated the butyrate-enhanced IL-22 generation, indicating HDACs were engaged in butyrate-regulated IL-22 secretion. In addition, butyrate triggered the STAT3/HIF-1α signaling to elevate the IL-22 expression in HKMs. Importantly, the evidence in vitro and in vivo was provided that butyrate activated Autophagy in fish macrophages via IL-22 signaling, which contributing to the elimination of invading bacteria. In conclusion, we clarified in the current study that butyrate induced STAT3/HIF-1α/IL-22 signaling pathway via GPCR binding and HDAC3 inhibition in fish macrophages to activate Autophagy that was involved in pathogen clearance in fish macrophages.

Keywords

Autophagy; Butyrate; GPCRs; HDAC3; IL-22; STAT3.

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