The Role of Neutrophils in Spondyloarthritis: A Journey across the Spectrum of Disease Manifestations

Abstract

Spondyloarthritis (SpA) contemplates the inflammatory involvement of the musculoskeletal system, gut, skin, and eyes, delineating heterogeneous diseases with a common pathogenetic background. In the framework of innate and adaptive immune disruption in SpA, neutrophils are arising, across different clinical domains, as pivotal cells crucial in orchestrating the pro-inflammatory response, both at systemic and tissue levels. It has been suggested they act as key players along multiple stages of disease trajectory fueling type 3 immunity, with a significant impact in the initiation and amplification of inflammation as well as in structural damage occurrence, typical of long-standing disease. The aim of our review is to focus on neutrophils' role within the spectrum of SpA, dissecting their functions and abnormalities in each of the relevant disease domains to understand their rising appeal as potential biomarkers and therapeutic targets.

Keywords: arthritis; enthesitis; inflammatory bowel disease; neutrophils; psoriasis; spondyloarthritis; uveitis.

Figure 1

Legend. Neutrophils are pleiotropic cells that play a central role in the very early phase of SpA development, contributing to triggering inflammation in multiple tissues. Neutrophils are recruited from the bloodstream to target sites in Spondyloarthritis (SpA), such as joints, entheses, gut, skin, and eyes, where they produce neutrophils extracellular traps (NETs), cytokines, and chemokines to attract and activate other immune cells, boosting type 3 immunity.