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Diamond Ling, Baoying Liu, Hatice N. Sen, Megan Casady, Zhiyu Li, Lai Wei, Shayma Jawad, Robert B. Nussenblatt; The Elevation Of Cd14high16+ Monocytes In Uveitis Patients. Invest. Ophthalmol. Vis. Sci. 2012;53(14):6313.
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© ARVO (1962-2015); The Authors (2016-present)
Reports have described the involvement of monocytes/macrophages in experimental autoimmune uveitis models and some subtypes of uveitis, such as sarcoidosis. This study characterizes subsets of monocytes in the peripheral blood of noninfectious uveitis patients.
Monocytes in whole blood from uveitis patients and control donors were characterized with surface cell staining and the relative percentages of monocyte subtypes were compared between patients and donors. The effects of dexamethasone, IL-4, LPS and IFNgamma on monocyte plasticity were performed in vitro and analyzed with flow cytometry. Cytokine expression in monocyte subsets was analyzed using real-time polymerase chain reactions (RT-PCR).
Human peripheral monocytes have three distinct subsets: CD14high16+, CD14high16-, and CD14dim16+. Uveitis patients exhibit higher levels of CD14high16+ monocytes compared to healthy controls. There were no significant differences in CD14high16+ monocytes among patients with different racial backgrounds, disease activity, or disease etiology. Monocytes treated with LPS and IFNgamma have higher CD14high16- expression, while, alternatively, IL-4 or dexamethasone stimulated cells display greater CD14high16+ expression. Furthermore, treatment of LPS and IFNgamma followed by dexamethasone (or vice versa) in vitro can shift the relative proportion of these subtypes, demonstrating that monocyte heterogeneity is plastic. Lastly, these CD14high16+ cells also express less pro-inflammatory cytokines such as TNFalpha, and IL-8, but expressed more anti-inflammatory IL-10.
CD14high16+ monocytes are more immunoregulatory than CD14high16- cells. In uveitis patients, the elevation of these cells may indicate a possible compensatory mechanism, and as such, implies an immunoregulatory role for monocytes/macrophages in uveitis pathogenesis.
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