The mucosal surfaces of both eyes are immunologically linked by a neurogenic inflammatory reflex involving TRPV1 and substance P

GUZMÁN, MAURICIO; MIGLIO, MAXIMILIANO S.; ZGAJNAR, NADIA R.; COLADO, ANA; ALMEJÚN, MARÍA B.; KEITELMAN, IRENE A.; SABBIONE, FLORENCIA; FUENTES, FEDERICO; TREVANI, ANALÍA S.; GIORDANO, MIRTA N.; GALLETTI, JEREMÍAS G.

MUCOSAL IMMUNOLOGY

NATURE PUBLISHING GROUP

Lugar: Londres; Año: 2018

1933-0219

Immunological interdependence between the two eyes has been reported for the cornea and the retina but not for the ocular mucosal surface. Intriguingly, patients frequently report ocular surface-related symptoms in the other eye after unilateral ocular surgery. Here we show how unilateral eye injuries in mice affect the mucosal immune response of the opposite ocular surface. We report that, despite the lack of lymphatic cross-drainage, a neurogenic inflammatory reflex in the contralateral conjunctiva is sufficient to increase, first, epithelial nuclear factor kappa B signaling, then, dendritic cell maturation, and finally, expansion of effector, instead of regulatory, T cells in the draining lymph node, leading to disrupted ocular mucosal tolerance. We also show that damage to ocular surface nerves is required. Using pharmacological inhibitors and agonists, we identified transient receptor potential vanilloid 1 (TRPV1) channel as the receptor sensing tissue damage in the injured eye and substance P released in the opposite ocular surface as the effector of the sympathetic response. Finally, blocking either step prevented subsequent ocular allergic reactions in the opposite eye in a unilateral corneal alkali burn model. This study demonstrates that both ocular surfaces are immunologically linked and suggests potential therapeutic targets for intervention.