Specific Induction of TSLP by the Viral RNA Analogue Poly(I:C) in Primary Epithelial Cells Derived from Nasal Polyps

Abstract

IntroductionChronic rhinosinusitis with nasal polyposis is an inflammatory disease that, although not directly linked to allergy, often displays a Th2-skewed inflammation characterized by elevated local IgE and IL-5 levels. The nasal cavity is constantly exposed to bacteria and viruses that may trigger epithelial inflammatory responses. To gain more insight into mechanisms by which such a biased inflammation might arise, we have investigated the epithelial expression of the Th2 skewing mediators (TSLP, IL-25, and IL-33) in relationship to disease and microbial triggers.MethodsEpithelial cells were obtained from polyp tissues of nasal polyposis patients and from inferior turbinates of non-diseased controls. Cells were exposed to various TLR-specific triggers to study the effect on mRNA and protein expression level of TSLP, IL-25, and IL-33 and the potential regulatory mechanisms through the expression profile the transcription factors ATF-3, DUSP-1, EGR-1, and NFKB-1.ResultsThe TLR3 agonist and viral analogue poly(I:C) induced TSLP mRNA 13.0 ± 3.1 fold (p < 0.05) and protein expression by 12.1 ± 2.3-fold (p < 0.05) higher in epithelium isolated from nasal polyposis patients than in epithelium form healthy controls. This enhanced induction of TSLP may be a consequence of a down-regulated expression of DUSP-1 in polyp epithelium.ConclusionThe TLR3 induced expression of TSLP introduces a mechanism by which the Th2-skewed tissue environment might arise in nasal polyps and invites a further evaluation of the potential contribution of current or past viral infections to polyposis pathogenesis.

Enhanced Type 2 Immune Reactions by Increased IL-22/IL-22Ra1 Signaling in Chronic Rhinosinusitis With Nasal Polyps

“…Moreover, previous studies revealed that the expression of TSLP was induced by poly(I:C) in nasal epithelial cells of NP. 27 Thus, we tested whether the IL-22/IL-22Ra1 axis could promote TSLP expression under poly(I:C) stimulation. NHBE cells stimulated with IL-4, IL-13, or IL-22 alone did not promote TSLP production ( Supplementary Fig.…”

<p>Chronic Rhinosinusitis with Nasal Polyps: Targeting IgE with Anti-IgE Omalizumab Therapy</p>

“…[49][50][51] A general knockdown of the T2 inflammatory axis is seen. 44 Viral rhinitis is a potent drive for CRSwNP 52 and omalizumab may prevent viral immune amplification of inflammatory pathways in CRSwNP. An important and novel finding with omalizumab treatment is improvement in innate viral defence.…”

Release of Type 2 Cytokines by Epithelial Cells of Nasal Polyps

“…TSLP and TSLP receptor have been found highly expressed in sinus mucosa of patients with CRSwNP [8–11], and a recent work by Golebski et al [22] was able to demonstrate that the TLR3 agonist and viral analog poly(I:C) were able to induce higher TSLP mRNA and protein expression in the epithelium isolated from nasal polyposis patients compared to epithelium form healthy controls, while a few and contrasting observations have been reported on the presence of IL-25 in CRS. IL-25 mRNA has been reported to be significantly elevated in ethmoid sinuses of CRSwNP compared to controls and CRSsNP by Lam et al [23].…”