Purchase this article with an account.
Nancy Reyes, Daniel R Saban; Pathogenesis of meibomian gland dysfunction (MGD) requires the T cell-neutrophil axis, in the allergy setting. Invest. Ophthalmol. Vis. Sci. 2016;57(12):1431.
Download citation file:
© ARVO (1962-2015); The Authors (2016-present)
Though an association between inflammation and MGD causation is well established, the immunopathogenesis remains poorly understood. One possibility considered herein involves a role for lymphocytes referred to as T helper 17 cells (Th17), which are generally known to mediate chronic inflammatory diseases. The latter is effected by their capacity to recruit/activate neutrophils (i.e. PMN) proficiently. To ask whether this Th17-PMN axis is relevant in MGD causation, we took advantage of our established model of severe allergic eye disease (AED). Typically 80% of these mice develop MGD, as revealed by terminal duct obstruction.
To induce AED (i.e. Severe-allergy), C57BL/6 mice were IP injected with ovalbumin (OVA) in aluminum hydroxide (alum) and pertussis toxin. In contrast, to induce allergic conjunctivitis (i.e. Mild-allergy), mice were IP injected with OVA and alum. Some Mild-allergy mice furthered received in vitro polarized Th17 vs. Th2 cells (OT-II) intravenously. After 14 d, mice were challenged topically with OVA for 7 d. Some Severe-allergy mice received systemic anti-IL-23 mAb (100 μg) 3 times per wk, beginning day before immunization and stopped before 1st challenge. Other Severe-allergy mice received anti-Ly6G mAb (500 μg) every other day during challenge period. Lymph nodes (LN) and conjunctivae were harvested after final challenge and analyzed by flow cytometry.
Results demonstrated that in the 80% of Severe-allergy mice that developed MGD, there was a significant expansion of Th17 cells (CD4+IL17+ IL-4/13-IFN-g +/-) in the LN and recruitment to the conjunctiva of PMN (CD45+Ly6G+Ly6C-Siglec F-). In contrast, none of the Mild-allergy mice developed MGD, and Th17 & PMN changes were not above naïve control levels. However, we were able to establish MGD and PMN recruitment in 80% of Mild-allergy mice by administration of Th17 polarized cells, but not Th2. We were also able to nearly abolish MGD onset and PMN recruitment in Severe-allergy mice via inhibition of Th17 cells (IL-23 blockade). The same was observed in Severe-allergy mice via PMN depletion (anti-Ly6G).
These data demonstrate that the Th17-PMN axis is necessary and sufficient to cause MGD, in the allergy setting. Our findings could explain the incidence of MGD in chronic allergy patients, and this pathway might be relevant to MGD pathobiology in other chronic inflammatory settings.
This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.
This PDF is available to Subscribers Only