Harnessing IL-22 for metabolic health: promise and pitfalls

Haressh Sajiir; Grant A Ramm; Graeme A Macdonald; Michael A McGuckin; Johannes B Prins; Sumaira Z Hasnain

doi:10.1016/j.molmed.2024.10.016

Harnessing IL-22 for metabolic health: promise and pitfalls

Trends Mol Med. 2024 Nov 21:S1471-4914(24)00283-1. doi: 10.1016/j.molmed.2024.10.016. Online ahead of print.

Authors

Haressh Sajiir¹, Grant A Ramm², Graeme A Macdonald³, Michael A McGuckin⁴, Johannes B Prins⁵, Sumaira Z Hasnain⁶

Affiliations

¹ Immunopathology Group, Mater Research Institute-The University of Queensland, Translational Research Institute, Brisbane, Australia; Faculty of Medicine, The University of Queensland, Brisbane, Australia.
² Faculty of Medicine, The University of Queensland, Brisbane, Australia; QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia.
³ Faculty of Medicine, The University of Queensland, Brisbane, Australia; Department of Gastroenterology and Hepatology, Princess Alexandra Hospital, Brisbane, Queensland, Australia.
⁴ Faculty of Medicine, Dentistry and Health Sciences, University of Melbourne, Parkville, Australia.
⁵ Faculty of Medicine, The University of Queensland, Brisbane, Australia; Health Translation Queensland, UQ Oral Health Building, Herston, Australia.
⁶ Immunopathology Group, Mater Research Institute-The University of Queensland, Translational Research Institute, Brisbane, Australia; Faculty of Medicine, The University of Queensland, Brisbane, Australia; Australian Infectious Disease Research Centre, The University of Queensland, Brisbane, Australia. Electronic address: [email protected].

PMID: 39578121
DOI: 10.1016/j.molmed.2024.10.016

Abstract

Primarily perceived as an anti-inflammatory and antimicrobial mediator in mucosa and skin, interleukin-22 (IL-22) has emerged as a pivotal metabolic regulator. Central to IL-22 signaling is its receptor, IL-22RA1. Through IL-22RA1, IL-22 orchestrates glucose homeostasis by modulating insulin secretion, reducing cellular stress in pancreatic islets, promoting beta-cell regeneration, and influencing hepatic glucose and lipid metabolism. These actions suggest its potential as a therapeutic for metabolic dysfunctions like diabetes, obesity, and steatohepatitis. However, clinical applications of IL-22 face challenges related to off-target effects and safety concerns. This review explores IL-22's physiological roles, regulatory mechanisms, and profound influence on metabolic tissues. It also underscores IL-22's dual role in metabolic health and disease, advocating further research to harness its therapeutic potential.

Keywords: IL-22RA1; diabetes; interleukin-22; liver; metabolism; obesity; pancreas; steatohepatitis.

Publication types

Review