The Interleukin-20 Cytokine Family in Liver Disease

Abstract

The three main causes of inflammation and chronic injury in the liver are viral hepatitis, alcohol consumption, and non-alcoholic steatohepatitis, all of which can lead to liver fibrosis, cirrhosis, and hepatocellular carcinoma, which in turn may prompt the need for liver transplant. The interleukin (IL)-20 is a subfamily part of the IL-10 family of cytokines that helps the liver respond to damage and disease, they participate in the control of tissue homeostasis, and in the immunological responses developed in this organ. The best-studied member of the family in inflammatory balance of the liver is the IL-22 cytokine, which on the one hand may have a protective role in fibrosis progression but on the other may induce liver tissue susceptibility in hepatocellular carcinoma development. Other members of the family might also carry out this dual function, as some of them share IL receptor subunits and signal through common intracellular pathways. Investigators are starting to consider the potential for targeting IL-20 subfamily members in liver disease. The recently explored role of miRNA in the transcriptional regulation of IL-22 and IL-24 opens the door to promising new approaches for controlling the local immune response and limiting organ injury. The IL-20RA cytokine receptor has also been classified as being under miRNA control in non-alcoholic steatohepatitis. Moreover, researchers have proposed combining anti-inflammatory drugs with IL-22 as a hepatoprotective IL for alcoholic liver disease (ALD) treatment, and clinical trials of ILs for managing severe alcoholic-derived liver degeneration are ongoing. In this review, we focus on exploring the role of the IL-20 subfamily of cytokines in viral hepatitis, ALD, non-alcoholic steatohepatitis, and hepatocellular carcinoma, as well as delineating the main strategies explored so far in terms of therapeutic possibilities of the IL-20 subfamily of cytokines in liver disease.

Intracellular XBP1-IL-24 axis dismantles cytotoxic unfolded protein response in the liver

“…A recent review has summarized the functions of IL-20 family cytokines in liver diseases 31 . IL-24 was suggested to function as a protective cytokine during liver inflammation through binding to its corresponding receptors.…”

Secretion of Recombinant Interleukin-22 by Engineered Lactobacillus reuteri Reduces Fatty Liver Disease in a Mouse Model of Diet-Induced Obesity

“…Indeed, IL-22 has several metabolic benefits, as it decreases chronic inflammation and regulates lipid metabolism in liver and adipose tissues (4,5). In mice, IL-22 elicits hepatoprotective properties via the activation of STAT3 (3,5,21); STAT3 downregulates the expression of lipogenic genes-and consequently reduces fat accumulation-and upregulates the expression of antiapoptotic genes, including reg3. Because the IL-22/STAT3/reg3 axis exists in the intestine (21), it is plausible that IL-22 upregulates REG3␤ and REG3␥ in jejunum via STAT3.…”

“…As of today, behavioral changes are considered the main driver to revert metabolic syndrome, but medical intervention strategies are considered the first line of treatment (2). In both nonalcoholic and alcoholic liver disease models, interleukin-20 (IL-20) family cytokines reduce liver injury and inflammation (3). For example, interleukin-22 (IL-22), a member of the IL-20 subfamily, controls lipid metabolism in the liver via activation of the STAT3 signaling pathway and, consequently, reduces fatty liver disease (4).…”

IL-22 ameliorates LPS-induced acute liver injury by autophagy activation through ATF4-ATG7 signaling

“…Interleukin-22 (IL-22), as one member of IL-10 cytokine family produced by T-helper (Th)17, Th22, natural killer (NK) cells, is involved in inflammatory reaction 3 , 4 . Extensive evidences indicated that IL-22 plays a protective role in epithelial tissues regeneration in response to infection 5 – 7 .…”