June 2021
Volume 62, Issue 8
Open Access
ARVO Annual Meeting Abstract  |   June 2021
Elucidating cytokine-mediated immunomodulation of NK cells in uveitis patients
Author Affiliations & Notes
  • Aman Kumar
    National Eye Institute, Bethesda, Maryland, United States
    Albany Medical College, Albany, New York, United States
  • Pulak Ranjan Nath
    National Eye Institute, Bethesda, Maryland, United States
  • Jung W Lee
    National Eye Institute, Bethesda, Maryland, United States
  • Mary Maclean
    National Eye Institute, Bethesda, Maryland, United States
  • Vrushali Vinay Agashe
    National Eye Institute, Bethesda, Maryland, United States
  • Mehmet Yakin
    National Eye Institute, Bethesda, Maryland, United States
  • H Nida Sen
    National Eye Institute, Bethesda, Maryland, United States
  • Footnotes
    Commercial Relationships   Aman Kumar, None; Pulak Nath, None; Jung Lee, None; Mary Maclean, None; Vrushali Agashe, None; Mehmet Yakin, None; H Nida Sen, None
  • Footnotes
    Support  None
Investigative Ophthalmology & Visual Science June 2021, Vol.62, 3465. doi:
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      Aman Kumar, Pulak Ranjan Nath, Jung W Lee, Mary Maclean, Vrushali Vinay Agashe, Mehmet Yakin, H Nida Sen; Elucidating cytokine-mediated immunomodulation of NK cells in uveitis patients. Invest. Ophthalmol. Vis. Sci. 2021;62(8):3465.

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

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Abstract

Purpose : Natural killer (NK) cells are a subset of lymphocytes that participate in the innate immune defense via their cytotoxic effector functions and cytokine secretion. NK cells play a role in the development of uveitis such as Behçet's uveitis. Additionally, several cytokines have been associated with promoting inflammation and contributing to the[KA([1] development of uveitis in both animals and humans. The purpose of this study is to understand the effect of cytokines relevant to human uveitis on NK cells.

Methods : Peripheral serum cytokines for 126 uveitis patients and 34 healthy controls were investigated using SOMAScan, an aptamer-based proteomics platform that measures over 1300 analytes. Human NK-92 cells were incubated with recombinant human cytokines that were relevant from the SOMAScan studies at previously titrated concentrations for 24 and 48 hours. At each timepoint, expression levels of several activation and inhibitory markers were characterized using a Cytoflex flow cytometer.

Results : SOMAscan proteomic analysis of serum showed elevated levels of certain cytokines, including interleukin (IL)-8, IL-9, IL-18Bpa, and IL-23 in the sera of uveitis subgroups. Flow cytometry from the peripheral blood of the same subgroup of patients also showed NK cell expansion. NK-92 cells demonstrated increased activation upon exposure to IL-12, IL-23 and IL-18, as indicated by elevated CD69 and CD314 expression after 24 hours. Additionally, there was a change in inhibitory receptor expression between the control and ED50 MFI, but to a lesser extent, illustrated by the level of CD94 expression.

Conclusions : The subset of cytokines previously identified to be associated with uveitis may play a role in immunomodulation of effector cells. We plan to further characterize the effect of these cytokines on human PBMCs and NK cells from uveitis patients and healthy controls.

This is a 2021 ARVO Annual Meeting abstract.

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