Thymic stromal lymphopoietin activity is increased in nasal polyps of patients with chronic rhinosinusitis

Abstract

Background Chronic rhinosinusitis with nasal polyps (CRSwNP) is associated with Th2-dominant inflammation. Thymic stromal lymphopoietin (TSLP) is a cytokine that triggers dendritic cell-mediated Th2 inflammatory responses and that enhances IL-1-dependent Th2 cytokine production in mast cells. Although elevated levels of TSLP mRNA have been found in nasal polyps (NPs), expression of TSLP protein and its function in CRS have not been fully explored. Objectives The objective of this study was to investigate the role of TSLP in CRS. Methods We investigated the presence and stability of TSLP protein in NPs by ELISA and western blot, and the function of TSLP in nasal tissue extracts with a bioassay based upon activation of human mast cells. Results Although TSLP mRNA was significantly increased in NP tissue from patients with CRSwNP compared to uncinate tissue from patients with CRS or control subjects, TSLP protein was significantly decreased in NP tissue as detected by the commercial ELISA kit. We found that recombinant TSLP was time-dependently degraded by NP extracts and this degradation was completely inhibited by a protease inhibitor cocktail, suggesting that TSLP is sensitive to tissue proteases. Interestingly, NP extract-treated TSLP had higher activity in mast cells, although the amount of full length TSLP was reduced up to 85%. NP extracts significantly enhanced IL-1β-dependent IL-5 production in mast cells compared with uncinate tissue homogenates, and responses were significantly inhibited by anti-TSLP, suggesting that NP contain biologically relevant levels of TSLP activity. Conclusion TSLP and its metabolic products may play an important role in the inflammation in CRSwNP.

Group 2 Innate Lymphoid Cells in Health and Disease

“…This study also showed that the ILC2s from CRS patients responded to IL-33-mediated stimulation by producing IL-13 (Shaw et al 2013), further suggesting that ILC2s may contribute to the pathogenesis of allergic upper airway disease in humans. Consistent with previous findings (Mjosberg et al 2012), TSLP has recently been shown to be highly expressed in the nasal polyps of CRS patients (Nagarkar et al 2013). Although IL-33 appears to be more potent than TSLP in activating type 2 cytokine production from nasal polyp ILC2s (Mjosberg et al 2012), further studies will be required to determine which cytokines optimally promote ILC2-mediated inflammation in CRS and whether these cells have a causal role in the development of nasal polyps or pathology in CRS patients.…”

Searching for Distinct Mechanisms in Eosinophilic and Noneosinophilic Airway Inflammation

“…TSLP expression was elevated only in eosinophilic polyps, which is consistent with previous reports investigating TSLP in polyps from patients in America (19), and it was positively correlated with levels of OX40L 1 DCs. This was not surprising because previous studies have shown that TSLP can directly induce OX40L expression on DCs (16).…”

International Consensus Statement on Allergy and Rhinology: Rhinosinusitis

“…538,539 The critical upstream epithelial cytokine is not completely clear, but high levels of TSLP activity have been identified in polyp homogenates. 540,541 Some evidence suggests that IL-33 may play a role as well, but these studies have yet to demonstrate increased expression of this cytokine at the protein level in NP tissue. 374,[542][543][544] In regard to IL-25, evidence in CRS is scant.…”