Il22ra2, encoding the IL-22 binding protein (IL-22BP), is a gene with significant biological importance. IL-22BP is a soluble decoy that decreases the bioavailability of interleukin 22 (IL-22), thus attenuating IL-22 signaling. IL-22 is involved in promoting intestinal barrier integrity and stimulating epithelial cells to defend against enteric infections, so Il22ra2 indirectly impacts these processes [1].

In gene knockout studies, Il22ra2-/-mice show enhanced protection against Clostridioides difficile and Citrobacter rodentium infections. This protection is due to IL-22-induced antimicrobial mechanisms before infection, and the gut microbiota of these knockout mice can mitigate infection in wild-type mice upon transfer. Resistance to C. difficile infection is related to increased acetate production by Il22ra2-/-associated microbiota [1].

In the context of multiple sclerosis, a rare coding variant rs28385692 in the IL22RA2 signal peptide coding region decreases the secretion of IL-22BP isoforms and is associated with an augmented risk for the disease [2]. Also, Il22ra2-/-mice have a less severe course of experimental autoimmune encephalomyelitis, with less demyelination and immune cell infiltration in the central nervous system, suggesting that lack of IL-22BP leads to higher IL-22 availability which has a protective effect in CNS inflammation [3].

In pneumococcal pneumonia, Il22ra2 deficiency favors down-regulation of oxidative phosphorylation genes in an IL-22-dependent manner, and Il22ra2-/-mice are more resistant to the infection [4].

In the bleomycin model of acute lung injury, Il22ra2-/-mice have greater sensitivity and pulmonary inflammation in the acute phase, driven by excess IL-22 production and the influx of pathogenic IL-17A+ γδ T cells to the lung [5].

In conclusion, Il22ra2 plays a crucial role in modulating IL-22 bioavailability and subsequent signaling, influencing host defense mechanisms. Gene knockout mouse models have revealed its significance in various disease areas such as enteric infections, multiple sclerosis, neuroinflammation, pneumococcal pneumonia, and acute lung injury. Understanding Il22ra2 can provide insights into disease mechanisms and potential therapeutic strategies.