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A role for neutrophils in early enthesitis in spondyloarthritis.

Authors:
Zheni Stavre Charles Bridgewood Qiao Zhou Yukiko Maeda Ting-Ting Huang Jozsef Karman Almas Khan Sami Giryes Kassem Sharif Dennis McGonagle Ellen M Gravallese

Arthritis Res Ther 2022 01 17;24(1):24. Epub 2022 Jan 17.

Department of Medicine/Division of Rheumatology, Inflammation and Immunity, Brigham and Women's Hospital, Boston, MA, 02115, USA.

Background: Neutrophils are present in the early phases of spondyloarthritis-related uveitis, skin and intestinal disease, but their role in enthesitis, a cardinal musculoskeletal lesion in spondyloarthritis, remains unknown. We considered the role of neutrophils in the experimental SKG mouse model of SpA and in human axial entheses.

Methods: Early inflammatory infiltrates in the axial and peripheral entheseal sites in SKG mice were evaluated using immunohistochemistry and laser capture microdissection of entheseal tissue. Whole transcriptome analysis was carried out using Affymetrix gene array MTA 1.0, and data was analyzed via IPA. We further isolated neutrophils from human peri-entheseal bone and fibroblasts from entheseal soft tissue obtained from the axial skeleton of healthy patients and determined the response of these cells to fungal adjuvant.

Results: Following fungal adjuvant administration, early axial and peripheral inflammation in SKG mice was characterized by prominent neutrophilic entheseal inflammation. Expression of transcripts arising from neutrophils include abundant mRNA for the alarmins S100A8 and S100A9. In normal human axial entheses, neutrophils were present in the peri-entheseal bone. Upon fungal stimulation in vitro, human neutrophils produced IL-23 protein, while isolated human entheseal fibroblasts produced chemokines, including IL-8, important in the recruitment of neutrophils.

Conclusion: Neutrophils with inducible IL-23 production are present in uninflamed human entheseal sites, and neutrophils are prominent in early murine spondyloarthritis-related enthesitis. We propose a role for neutrophils in the early development of enthesitis.

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http://dx.doi.org/10.1186/s13075-021-02693-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8762869PMC
January 2022

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