High Dimensional Analysis of PBMC in Axial Spondyloarthritis Reveals that S100A8 ^hi Monocyte Derived CXCL8 Mediates Neutrophil Recruitment

Abstract

SUMMARY Although the inflammatory response plays a critical role in the pathogenesis of axial spondyloarthritis (SpA), the precise immune cell subset involved in axial SpA remains less well defined. In this study, we found that the percentages of peripheral granulocytes and monocytes were significantly higher in axial SpA patients. Among monocytes, a subset of S100A8^hi expressing monocytes had markedly high levels of inflammatory and chemotactic characteristics. Furthermore, a potential interaction between S100A8^hi monocytes and granulocytes via the CXCL8-CXCR1/2 signaling pathway was explored. Importantly, following therapy, not only were the interactions between monocytes and granulocytes significantly reduced, but the frequencies of granulocytes were also reduced in the peripheral blood of axial SpA patients. Our findings suggest that the interactions between monocytes and granulocytes plays an important role in the pathogenesis of axial SpA. In particular, S100A8^hi monocyte derived CXCL8 mediates granulocytes recruitment in the peripheral blood of axial SpA patients.

Keywords: Axial Spondyloarthritis, Monocytes, anti-TNF therapy, Single cell