Mucosal immune tolerance at the ocular surface in health and disease

Abstract

SummaryThe ocular surface is constantly exposed to environmental irritants, allergens and pathogens, against which it can mount a prompt immune response to preserve its integrity. But to avoid unnecessary inflammation, the ocular surface's mucosal immune system must also discriminate between harmless and potentially dangerous antigens, a seemingly complicated task. Despite its unique features, the ocular surface is a mucosal lining, and as such, it shares some homeostatic and pathophysiological mechanisms with other mucosal surfaces. The purpose of this review is to explore the mucosal homeostatic immune function of the ocular surface in both the healthy and diseased states, with a special focus on mucosal immunology concepts. The information discussed in this review has been retrieved by PubMed searches

Transient tear hyperosmolarity disrupts the neuroimmune homeostasis of the ocular surface and facilitates dry eye onset

“…Although the role of the adaptive immune response in DED pathophysiology is firmly established, 43,[52][53][54] the actual, either self-or non-self-derived ocular surface antigens involved remain unknown. 17 This limitation, which precludes direct exploration of antigen-specific immune responses, was overcome in our model by imbibing the ocular surface with an exogenous inert antigen. Thus, we probed the physiological response to it, i.e.…”

“…Because the antigen specificity of the T-cells responsible for corneal damage in DED is unknown, 17 we imbibed the eyes with an inert exogenous protein, OVA, to serve as a surrogate ocular surface antigen that allowed us to track the antigen-specific immune response. Under non-DED conditions, mice exposed to OVA eye drops develop OVA-specific regulatory T-cells that reduce subsequent immunization with the same antigen.…”

“…This homeostatic mechanism is termed mucosal tolerance because it prevents unwanted inflammation against the harmless foreign antigens to which mucosal linings are continuously exposed. 17,39 We have previously observed that mice must be exposed to desiccating stress over 3 days before they lose ocular mucosal tolerance to OVA, 21,22 that is, they develop OVA-specific effector T-cells instead of regulatory T-cells. Therefore, in this setup, we also deferred the instillation of OVA by 3 days to allow for a potentially similar disruptive effect to take place but induced instead by THO ( Fig.…”

“…This is so because a set of homeostatic mechanisms prevent unwanted, potentially damaging inflammation from arising in response to challenges that do not pose a threat. 17 This phenomenon is experimentally known as mucosal tolerance, and involves the generation of antigen-specific regulatory T-cells that suppress inflammation. [17][18][19] Loss of ocular mucosal tolerance (and, thus, of mucosal immune homeostasis) has been implicated in other ocular inflammatory disorders, such as eye drop preservative toxicity 19 and allergic conjunctivitis.…”

“…17 This phenomenon is experimentally known as mucosal tolerance, and involves the generation of antigen-specific regulatory T-cells that suppress inflammation. [17][18][19] Loss of ocular mucosal tolerance (and, thus, of mucosal immune homeostasis) has been implicated in other ocular inflammatory disorders, such as eye drop preservative toxicity 19 and allergic conjunctivitis. 20 Moreover, we have previously shown that in conventional murine models of DED, a disruption in ocular mucosal tolerance eventually ensues and contributes to ocular surface damage.…”