T helper cytokines in dry eye disease

Abstract

Dry eye is an inflammatory disease that results from activation of innate inflammatory pathways in resident ocular surface cells, as well as cytokines produced by recruited T helper (Th) cells. Cytokines produced by the infiltrating Th cells alter the normal cytokine balance on the ocular surface and cause ocular surface epithelial pathology. Changes in levels of Th cytokines on the ocular surface have been measured in dry eye and the biological effects of these cytokines have been documented in experimental culture and mouse model systems. The Th2 cytokine IL-13 has a homeostatic role in promoting goblet cell differentiation. In contrast, The Th1 cytokine IFN-γ antagonizes IL-13 and promotes apoptosis and squamous metaplasia of the ocular surface epithelia. The Th17 cytokine, IL-17 promotes corneal epithelial barrier disruption. The ocular surface epithelium expresses receptors to all of these Th cytokines. Therapies that maintain normal IL-13 signaling, or suppress IFN- γ and IL-17 have potential for treating the ocular surface disease of dry eye.

Goblet cell loss abrogates ocular surface immune tolerance

“…Loss of tolerance in the dry eye group was confirmed by increased DTH to OVA antigen, reduced T cell suppression of antigen-specific T cell proliferation, and increased generation of IFN-γ-and IL-17-positive CD4 + T cells (10). Both of these T helper cytokines have been implicated in the pathogenesis of the ocular surface epithelial disease that develops in dry eye (6,23,25).…”

The role and treatment of inflammation in dry eye disease

“…Regulatory T cells (Treg) and various anti-inflammatory factors which are present on the ocular surface and tears have an antagonizing effects on pro-inflammatory cytokines that were initiated by immature APCs following an insult to the ocular surface [4,11,12]. Among protective immunoregulatory mediators, Th cytokine IL-13 has homeostatic role in promoting goblet cell differentiation, and transforming growth factor (TGFb) suppresses activation of ocular surface dendritic cells [6,13].…”

“…T (Th17), play a central role in immune mechanisms [3,4,14]. Goblet cell loss due to inflammation additionally causes disruption of tear function and a reduction in suppression of the immune reactions [3,4,6,14].…”

“…Many factors causing ocular surface damage and inflammation have been shown to contribute to these mechanisms. The common mechanism shown in all DED types is chronic inflammation stimulated by the activation of innate immune components in ocular surface cells, decrease in tear film stability, and increase in tear osmolarity [1,[3][4][5][6][7][8].…”

Evaluation of the expression of T helper lymphocytes markers associated with Th1, Th2, Th17, and Treg cells in primary pterygium biopsies

“…Algunos estudios sugieren que IL-13 es la citocina Th2 predominante en la superficie ocular normal, razón por la cual encontramos una expresión basal en los tejidos que puede modificarse al aumentar el grado de extensión de Pt 14 . Por otro lado, se ha descrito en biopsias de Pt obtenidas de pacientes atópicos y no atópicos un aumento significativo en la expresión de IL-4 y una disminución evidente de IFN-γ, lo que concuerda con los resultados observados en nuestras muestras 15 .…”