POS0432 MDSCs IN THE INFLAMMATORY JOINT OF SKG MICE HAVE BOTH T CELL SUPPRESSIVE ABILITY AND OSTEOCLAST DIFFERENTIATION POTENTIAL

Y. Fujikawa, S. Sendo, T. Nagamoto, Y. Yamamoto, H. Yamada, T. Okano, K. Nishimura, Y. Ueda, J. Saegusa
2022 Annals of the Rheumatic Diseases  
BackgroundMyeloid-derived suppressor cells (MDSCs) are heterogeneous immature myeloid cells with suppressive functions (1). It is known that MDSCs are expanded in inflammatory sites after migrating from bone marrow (BM) or spleen. Rheumatoid arthritis (RA) is an autoimmune disease characterized as polyarthritis. Although previous reports indicate that MDSCs are increased in BM and spleen of arthritis model mice, detailed analysis of MDSCs in inflammatory joints is limited.ObjectivesThe purpose
more » ... f this study is to characterize the MDSCs in the joints of autoimmune arthritis.MethodsWe isolated CD11b+Gr1+ cells as MDSCs from joints (Jo-MDSCs), bone marrow (BM-MDSCs) and spleen (Sp-MDSCs) of arthritis-induced SKG mice, and investigated differential expressed genes (DEGs) among MDSCs from three tissues by microarray expression analysis. Furthermore, we analyzed the suppressive function of each MDSCs by investigating the effect of them on T cell -proliferation and the osteoclast differentiation of each MDSCs stimulated by M-CSF and RANKL.ResultsMicroarray analysis revealed that Jo-MDSCs highly expressed immunosuppressive DEGs (Pdl1, Arg1, Egr2 and Egr3) compared to BM MDSCs or Sp MDSCs. In addition, Jo-MDCSs highly expressed NF-κB non-canonical pathway DEGs (Nfkb2 and Relb), which are related to osteoclast differentiation. BM-MDSCs differentiated into osteoclasts but didn't suppress T cell-proliferation and Sp-MDSCs suppressed T cell-proliferation but didn't differentiate into osteoclasts. On the other hand, Jo-MDSCs was found to have both functions: T cell suppression and osteoclast differentiation potential.ConclusionJo-MDSCs have a strong inhibitory effect on T cell proliferation and have the ability osteoclast differentiation potential.References[1]Veglia F, Perego M, Gabrilovich D. Myeloid-derived suppressor cells coming of age. Nat Immunol. 2018;19(2):108–19.Disclosure of InterestsNone declared.
doi:10.1136/annrheumdis-2022-eular.3373 fatcat:iijnth36t5b2filoqecuxaztj4