Purchase this article with an account.
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.
Download citation file:
© ARVO (1962-2015); The Authors (2016-present)
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.
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.
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.
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.
This PDF is available to Subscribers Only