Session Information
Session Type: ACR Poster Session B
Session Time: 9:00AM-11:00AM
Background/Purpose:
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 signaling in lymphoid cells is associated with IL-22 production and since IL-22 is a pivotal cytokine that maintains gut and skin stem cell function1,2, we hypothesized 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).
Methods:
Human Bone marrow MSCs were expanded and tested by multi-parameter flow cytometry for expression of the ISCT criteria for MSCS and IL-22R. IL-22R priming was undertaken with IFN gamma and TNF alpha prior to recombinant IL-22 exposure. 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 in combination with IFN gamma and TNF alpha, Mean fluorescent intensity (MFI) increased 1.8±0.12 fold. MSCs proliferation and migration dramatically increased following IL-22 exposure after IFN gamma and TNF alpha combined priming compared to IL-22 alone or no cytokine (p= 0.0159 and 0.028). MSCs migration function was enhanced by IL-22 after priming with IFN gamma and TNF alpha compared to no cytokine (p= 0.0159). Osteogenic differentiation was significantly higher in MSCs exposed to IL-22 alone (p=0.002), but was depressed when IL-22 combined with IFN gamma and TNF alpha compared to IL-22 alone or no cytokine (p=0.002 and p=0.003).
Conclusion:
Given that IL-22 is exclusively produced by lymphoid cells and acts on non-lymphoid 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 IFN gamma & TNF alpha in vitro and had variable effects depending on the inflammatory milieu. Given the IL23 axis association with SpA this work opens up a novel pathway for exploring new bone formation in SpA related disease.
To cite this abstract in AMA style:
El-Sherbiny Y, Elzayadi A, Fragkakis EM, Cuthbert R, Baboolal T, Jones E, McGonagle D. IL-22 Drives the Proliferation and Differentiation of Human Bone Marrow Mesenchymal Stem Cells (MSCs); A Novel Pathway That May Contribute to Aberrant New Bone Formation in Human Spa and Beyond [abstract]. Arthritis Rheumatol. 2015; 67 (suppl 10). https://acrabstracts.org/abstract/il-22-drives-the-proliferation-and-differentiation-of-human-bone-marrow-mesenchymal-stem-cells-mscs-a-novel-pathway-that-may-contribute-to-aberrant-new-bone-formation-in-human-spa-and-beyond/. Accessed .« Back to 2015 ACR/ARHP Annual Meeting
ACR Meeting Abstracts - https://acrabstracts.org/abstract/il-22-drives-the-proliferation-and-differentiation-of-human-bone-marrow-mesenchymal-stem-cells-mscs-a-novel-pathway-that-may-contribute-to-aberrant-new-bone-formation-in-human-spa-and-beyond/