Context-Dependent Regulation of Conjunctival Goblet Cell Function by Allergic Mediators

Laura García-Posadas,Darlene A Dartt,Robin R Hodges,Yolanda Diebold

doi:10.1038/s41598-018-30002-x

Abstract

In the eye, goblet cells responsible for secreting mucins are found in the conjunctiva. When mucin production is not tightly regulated several ocular surface disorders may occur. In this study, the effect of the T helper (Th) 2-type cytokines IL4, IL5, and IL13 on conjunctival goblet cell function was explored. Goblet cells from rat conjunctiva were cultured and characterized. The presence of cytokine receptors was confirmed by Reverse Transcription-Polymerase Chain Reaction (RT-PCR). Changes in intracellular [Ca2+], high molecular weight glycoconjugate secretion, and proliferation were measured after stimulation with Th2 cytokines with or without the allergic mediator histamine. We found that IL4 and IL13 enhance cell proliferation and, along with histamine, stimulate goblet cell secretion. We conclude that the high levels of IL4, IL5, and IL13 that characterize allergic conjunctivitis could be the reason for higher numbers of goblet cells and mucin overproduction found in this condition.

Highlights

Goblet cells are specialized cells that produce and secrete mucins that lubricate and protect mucosal tissues, maintaining their health[1,2]
To determine if conjunctival goblet cells were able to directly respond to the selected cytokines, receptors (R) for those cytokines were studied by Reverse Transcription-Polymerase Chain Reaction (RT-PCR)
Our results demonstrate that Th2 cytokines increased in several conjunctival, especially allergic, diseases have a direct effect on conjunctival goblet cell function

Summary

Introduction

Goblet cells are specialized cells that produce and secrete mucins that lubricate and protect mucosal tissues, maintaining their health[1,2]. Goblet cells are found in the epithelial layer of the conjunctiva. The amount of MUC5AC found in the ocular surface is tightly controlled by goblet cell number, MUC5AC synthesis, and MUC5AC secretion. One important inflammatory mediator present in allergy is histamine that in the conjunctiva is secreted by mast cells recruited into the stroma[6]. For H1, H3, and H4 histamine activates phospholipase C to release [Ca2+]i that induces the influx of extracellular Ca2+ This influx activates ERK1/2 to stimulate conjunctival goblet cell secretion[9]. One of the major sources of cytokines is T helper (Th) lymphocytes These Th cells can be divided in different subsets, such as Th1, Th2, Th17, or the most recently described Th22-type, and the cytokines are divided. We recently showed the role of interferon gamma (IFN-γ), the major Th1 cytokine, in goblet cell function modulation[14]

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