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Nancy Reyes, Preeya Gupta, Daniel Saban; A core role for T cells in meibomian gland dysfunction. Invest. Ophthalmol. Vis. Sci. 2017;58(8):990.
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© ARVO (1962-2015); The Authors (2016-present)
Involvement of the immune response may be a core pathogenesis pathway in many forms of meibomian gland dysfunction (MGD), as suggested by the common appearance of this condition in patients with underlying immunologic disease. We addressed this question using our established model of chronic allergic eye disease (AED) in which 80% of these mice develop MGD. Specifically, we asked whether T cells are important in causation and whether similar evidence of T cell involvement may be detectable in patients.
Adult IL-17A-/- (KO) and IL-17+/- (Het) mice were compared to C57BL/6 (WT) controls. The AED model was induced in these mice via single IP injection of ovalbumin (OVA) in alum and pertussis toxin, followed by topical OVA instillation. Lymph nodes (LN) and conjunctivae were harvested after final challenge and analyzed by flow cytometry. For human studies, we excluded MGD patients on systemic anticoagulative or immunosuppressive drugs within two weeks, or history of ocular surgery in the past 3 months of participation. Peripheral blood mononuclear cells (PBMCs) were isolated and analyzed by flow cytometry.
Our previous findings suggested that Th2 and Th1 cells are not sufficient to mediate MGD in AED mice, whereas Th17 cells are. In the current study, we confirmed that Th17 cells were significantly reduced in KO mice, as compared to WT controls. Strikingly, this reduction in Th17 cells correlated with a complete abolishment of MG plugging in AED, as 100% of the WT controls developed plugging. Furthermore, Het mice showed reduced plugging, as compared to WT controls. Interestingly, corresponding with these findings, in patients with MGD (n=4 patients), 50% of subjects showed increased Th17 frequencies in the peripheral blood, whereas healthy control patients did not (n=6).
These data demonstrate in mice that Th17 cells are necessary for the development of MGD, in the AED model. Our findings may also suggest that Th17 cells play a role in mediating MGD in a subset of patients. The implication of our data that immune cells contribute to the core pathogenic mechanism in MGD is particularly novel and may pave the way for novel treatments that reduce disease burden in certain patients.
This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.
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