IL-22 attenuates induced inflammation, apoptosis and tissue injury by regulating the ROS/NLRP3 inflammasome axis.

Zhensheng Wang, Wenya Zhai, Hong Liu
Author Information
  1. Zhensheng Wang: College of Fisheries, Key Lab of Freshwater Animal Breeding, Ministry of Agriculture and Rural Affair/Key Lab of Agricultural Animal Genetics, Breeding and Reproduction of Ministry of Education, Huazhong Agricultural University, Wuhan, China.
  2. Wenya Zhai: College of Fisheries, Key Lab of Freshwater Animal Breeding, Ministry of Agriculture and Rural Affair/Key Lab of Agricultural Animal Genetics, Breeding and Reproduction of Ministry of Education, Huazhong Agricultural University, Wuhan, China.
  3. Hong Liu: College of Fisheries, Key Lab of Freshwater Animal Breeding, Ministry of Agriculture and Rural Affair/Key Lab of Agricultural Animal Genetics, Breeding and Reproduction of Ministry of Education, Huazhong Agricultural University, Wuhan, China.

Abstract

Mammalian interleukin-22 (IL-22) attenuates organismal injury by inhibiting reactive oxygen species (ROS) and impeding the NLRP3 inflammasome activation. However, the role of fish IL-22 in this process remains unclear. We characterized MaIL-22, an IL-22 homolog in blunt snout bream (). Despite its low sequence identity, it shares conserved structures and close evolutionary relationships with other teleost IL-22s. Furthermore, () infection leads to tissue injury in immune organs and concomitantly altered mRNA expression, suggesting that MaIL-22 was involved in the antimicrobial immune response. To explore MaIL-22's biological functions, we produced recombinant MaIL-22 (rMaIL-22) protein and demonstrated it significantly enhanced the survival of post- infection. To unravel its protective mechanisms, we explored the ROS/NLRP3 inflammasome axis and its downstream signaling responses. The results showed that rMaIL-22 treatment significantly elevated antioxidant enzyme (T-SOD, CAT and GSH-PX) activities to inhibit MDA activity and scavenge ROS in visceral tissues. Meanwhile, rMaIL-22 impeded the activation of NLRP3 inflammasome by suppressing NLRP3 protein and mRNA expression. This indicated that rMaIL-22 contributed to inhibit -induced activation of the ROS/NLRP3 inflammasome axis. Consistent with these findings, rMaIL-22 treatment attenuated the expression of proinflammatory cytokines (, and ) and proapoptotic genes ( and ) while promoting antiapoptotic genes ( and ) expression, ultimately mitigating tissue injury in visceral tissues. In conclusion, our research underscores MaIL-22's key role in microbial immune regulation, offering insights for developing IL-22-targeted therapies and breeding programs.

Keywords

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MeSH Term

Animals
Aeromonas hydrophila
NLR Family, Pyrin Domain-Containing 3 Protein
Inflammasomes
Apoptosis
Gram-Negative Bacterial Infections
Reactive Oxygen Species
Interleukins
Fish Diseases
Interleukin-22
Inflammation
Fish Proteins
Cyprinidae
Signal Transduction

Chemicals

NLR Family, Pyrin Domain-Containing 3 Protein
Inflammasomes
Reactive Oxygen Species
Interleukins
Interleukin-22
Fish Proteins

Word Cloud

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