July 2019
Volume 60, Issue 9
Open Access
ARVO Annual Meeting Abstract  |   July 2019
Conventional and Non-conventional Lymphocytes exhibit dysregulated IL-22 and GM-CSF production in Acute Anterior Uveitis and Ankylosing Spondylitis
Author Affiliations & Notes
  • Jerry Chien-Chieh Huang
    Ophthalmology, Casey Eye Institute, OHSU, Portland, Oregon, United States
    Ophthalmology, Chang Gung Memorial Hospital, Keelung City, Taiwan
  • Matthew Schleisman
    Medicine, Division of Arthritis and Rheumatic Disease, OHSU, Portland, Oregon, United States
  • Claire Mitchell
    Medicine, Division of Arthritis and Rheumatic Disease, OHSU, Portland, Oregon, United States
    Ophthalmology, Casey Eye Institute, OHSU, Portland, Oregon, United States
  • Lindsey Watson
    Medicine, Division of Arthritis and Rheumatic Disease, OHSU, Portland, Oregon, United States
    Ophthalmology, Casey Eye Institute, OHSU, Portland, Oregon, United States
  • James T Rosenbaum
    Medicine, Division of Arthritis and Rheumatic Disease, OHSU, Portland, Oregon, United States
    Ophthalmology, Casey Eye Institute, OHSU, Portland, Oregon, United States
  • MARK ASQUITH
    Medicine, Division of Arthritis and Rheumatic Disease, OHSU, Portland, Oregon, United States
    Ophthalmology, Casey Eye Institute, OHSU, Portland, Oregon, United States
  • Footnotes
    Commercial Relationships   Jerry Huang, None; Matthew Schleisman, None; Claire Mitchell, None; Lindsey Watson, None; James Rosenbaum, None; MARK ASQUITH, None
  • Footnotes
    Support  None
Investigative Ophthalmology & Visual Science July 2019, Vol.60, 1725. doi:https://doi.org/
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      Jerry Chien-Chieh Huang, Matthew Schleisman, Claire Mitchell, Lindsey Watson, James T Rosenbaum, MARK ASQUITH; Conventional and Non-conventional Lymphocytes exhibit dysregulated IL-22 and GM-CSF production in Acute Anterior Uveitis and Ankylosing Spondylitis. Invest. Ophthalmol. Vis. Sci. 2019;60(9):1725. doi: https://doi.org/.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose : Underlying immune mechanisms that drive the HLA-B*27-associated inflammatory diseases acute anterior uveitis (AAU) and Ankylosing Spondylitis (AS) are incompletely understood. Recent studies have implicated RORγt-dependent immune signatures in the pathogenesis of related inflammatory diseases. In this study we developed a novel multi-parametric flow cytometry panel to identify immune dysregulation of these signatures in AAU or AS.

Methods : Peripheral Blood Mononuclear cells (PBMC) were isolated from AAU patients, AAU patients with concomitant spondylitis or healthy controls(n=9-12/group). Cells were polyclonally stimulated and subjected to flow cytometry. Antibody panels analyzed cytokine production (IFNγ, IL-17A, IL-17F, IL-22 and GM-CSF) by conventional CD4/CD8 T cells; or Mucosal-Associated Invariant T (MAIT) cells and type 3 innate lymphoid cells (ILC3). Data were analyzed in FlowJo (Tree star Inc.). Kruskall-Wallis test with Dunn’s correction for multiple comparisons was used for statistical analysis.

Results : Unexpectedly, we observed a significantly increased frequency of GM-CSF+ve CD8 T cells in AAU patients vs healthy controls, and a similar trend in GM-CSF production amongst CD4 T cells. Amongst non-conventional lymphocytes, MAIT cells exhibited markedly increased GM-CSF and IL-17A production in AAU patients with concomitant spondylitis, although not in those with AAU alone. We observed equivalent production of RORγt-dependent cytokines within the infrequent ILC3 population and found increased IL-22 production in the ILC3 population in those with AAU + AS. A significantly increased frequency of IL-22+ve CD8+ T cells was also observed in those with AAU alone.

Conclusions : Our data reveal that dysregulated RORγt-dependent cytokines GM-CSF and IL-22 are highly dysregulated in multiple circulating immune cell subsets in AAU. This is the first study to implicate 2 mucosal populations, MAIT and ILC-3 cells, in AAU and is consistent with a gut-eye axis contributing to AAU.

This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.

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