Intrinsic lipid mediator circuits: keys regulators of ocular adaptive immune responses

Abstract

Presentation Description : Lipoxins are the founding members of the specialized pro-resolving lipid mediators (SPM) and have important roles in controlling acute inflammation and promoting wound healing in the cornea. Our understanding of lipoxins roles in adaptive and T cell driven immune responses in the eye and during homeostasis are less clear and evolving. We have discovered a population of resident PMN in draining lymph nodes that generate lipoxins in healthy animals. The lymph node lipoxin circuit is regulated sex-specifically and by dietary DHA. Female-specific downregulation of the resident lymph node LXA₄ circuit as part of routine immune responses enables amplified effector T cell activation and is a determinant for immune-driven eye disease. Sex-specific and estrogen regulation of LXA₄ circuits at the site of initiating and amplifying adaptive immune responses maybe a mechanism for the striking high prevalence of female immune-driven eye diseases. The draining lymph node lipoxin circuit is a key factor in regulating effector T (T_H1, T_H17) and T regulatory (T_reg) cells in both corneal and retinal adaptive immune responses. These intrinsic lipoxin circuits are not limited to draining lymph nodes but are also expressed in astrocytes in the healthy retina. Our research provides evidence for tissue specific and resident lipoxin circuits that regulate routine T cell responses and have a role in maintaining neuronal homeostasis.

This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.