Ocular microflora modulates IL-17 and neutrophil recruitment within the conjunctiva associated lymphoid tissue (MUC9P.739)

Abstract

Abstract Previous studies have suggested a critical role for the functionality of conjunctiva‑associated lymphoid tissue (CALT), a mucosal immune tissue of the ocular surface, to maintain anterior ocular health. In this study, we developed a working animal model to study the functional properties of CALT in WT B6 and interleukin (IL)-22 KO mice, which are known to have impaired barrier function at gut mucosal surfaces. Aged IL-22 KO mice spontaneously developed CALT neutrophilia resulting in opacification of the cornea (keratitis). Neutrophilia in the CALT depended on in situ production of IL-17A/F, and was significantly reduced 48 hours after a single subconjunctival injection of αIL-17A/F. Innate lymphoid cells (ILCs) as well as αβ and γδ T cells isolated from CALT produced IL-17 in response to IL-1β made by activated CD11b+ dendritic cells, suggesting a role for normal ocular microflora in modulating mucosal immune responses at the ocular surface. Indeed, wild type mice treated with topical or oral antibiotics as well as germfree mice had reduced IL-17 and neutrophils in CALT. Our data uncover an interdependence between the CALT and normal ocular microflora for regulating mucosal immune function at the ocular surface and demonstrate its importance for maintaining long-term ocular surface homeostasis.