Background and objectives The human spondyloarthropathies (SpA) are associated with single nucleotide polymorphisms (SNPs) in the IL-23 pathway and IL-23/17 axis therapy is effective in SpA. The SpAs are also associated with new bone formation that is to a degree independent of TNF blockade. Given that IL-23R receptor signalling in lymphoid cells is associated with IL-22 production and since IL-22 is a pivotal cytokine that maintains gut and skin stem cell function,1,2 we hypothesised that IL-22 might also drive skeletal stem cells and hence contribute to the SpA bone phenotype. Therefore we explored the effect of IL-22 on bone marrow mesenchymal stem cells (MSCs).
Materials and methods Human Bone marrow MSCs were expanded and tested by flow cytometry for IL-22R expression. MSC proliferation and migration were tested by colorimetric XTT assay and chamber migration assays. MSC osteogenic functional differentiation was performed with and without cytokines.
Results MSCs expressed low level IL22RA1 which was significantly up-regulated (1.8 ± 0.12 fold) in combination with IFNG and TNFa. MSCs proliferation and migration dramatically increased following IL-22 exposure after IFNG and TNFa combined priming compared to IL-22 alone or no cytokine. MSCs migration function was enhanced by IL-22 after priming with IFNG and TNFa compared to no cytokine. Osteogenic differentiation was significantly higher in MSCs exposed to IL-22 alone, but decreased when IL-22 combined with IFNG and TNFa.
Conclusion IL-22 is exclusively produced by immune cells and acts on non-immune cells including stem cells; our findings confirm that IL-22 can drive bone marrow MSC osteogenesis. Furthermore, IL-22 boosted MSCs proliferation and migration after priming with IFNG & TNFa in vitro and had variable effects depending on the inflammatory milieu. Given that the IL-23 axis association with SpA this work opens up a novel pathway for exploring new bone formation in SpA related disease.
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Serafini et al. J Exp Med. 2014;211(2):199–208
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