Preliminary Report on Interleukin-22, GM-CSF, and IL-17F in the Pathogenesis of Acute Anterior Uveitis

ABSTRACT

Purpose:Anterior uveitis is the most common anatomic subset of uveitis. We developed a novel multi-parametric flow cytometry panel to identify immune dysregulation signatures in HLA B27-associated acute anterior uveitis (AAU) and axial spondyloarthritis (AxSpA).

Methods: We used fluorescence activated cell sorting to characterize T cell cytokine expression in stimulated T cell subsets from patients with AAU (n = 4) compared to healthy controls (n = 14) or subjects with AxSpA (n = 6).

Results: Positive findings among subjects with AAU included a statistically significant increase in stimulated granulocyte-macrophage colony stimulating factor (GM-CSF), IL-17, and IL-22 synthesized by CD8 cells, a trend for stimulated ILC (innate lymphoid cells)-3 cells to synthesize more IL-22 (p = .07), and stimulated MAIT (mucosa associated innate lymphoid cells)-like cells that express the T cell receptor V alpha 7.2 to express IL-17A, IL-17F, and IL-22 in a greater percentage of cells relative to controls. IL-17F, GM- CSF, and IL-22 represent potentially novel targets in AAU.

Conclusion: Our report is arguably the first to implicate IL-17F or ILC-3 and MAIT cells in the pathogenesis of AAU.

Abbreviations AAU: acute anterior uveitis; AxSpA: axial spondyloarthritis; BASDAI: Bath ankylosing spondylitis disease activity index; CCR: chemokine receptor; DMSO: dimethylsulfoxide; EULAR:European League Against Rheumatism; FACS: fluorescence activated cell sorter; FBS: fetal bovine serum; FSC: orward light scatter; GM-CSF: granulocyte-macrophage colony stimulating factor; HC: healthy control; ILC: innate lymphoid cell; KIR: killer immunoglobulin receptor; MAIT: mucosal associated immune T cell; ND: not detected; NK: natural killer cell; OHSU-Oregon Health & Science University; PBMC: peripheral blood mononuclear cell; SSC: side light scatter; TCR: T cell receptor.

KEYWORDS:

• Acute anterior uveitis
• spondyloarthritis
• cytokine
• interleukin
• innate lymphoid cell
• MAIT cell

Acknowledgments

We are grateful to Tammy Martin and Stephen Planck who provided assistance with formatting.

Declaration of interest

The authors declare no competing interests. Unrelated to this report, Dr. Rosenbaum receives clinical trial support from Pfizer, royalties from UpToDate, and consulting fees from AbbVie, Gilead, Janssen, Novartis, Roche, Celldex, Corvus, Horizon, and UCB.

Additional information

Funding

This study was funded in part by NIH Grant, [EY 029266, EY026572, and EY010572]. We also acknowledge support from the William and Mary Bauman Family Foundation, the Stan and Madelle Rosenfeld Family Trust, Research to Prevent Blindness, and the Grandmaison Fund for Autoimmunity Research. The funding sources were not involved in the collection or interpretation of data and they did not participate in the writing of this manuscript.