Release of Type 2 Cytokines by Epithelial Cells of Nasal Polyps

Abstract

Background. T2 inflammation of chronic rhinosinusitis with nasal polyps (CRSwNP) may be influenced by epithelial cytokines release (TSLP, IL-25, and IL-33). We investigated the release of TSLP, IL-25, and IL-33 by epithelial CRSwNP cells compared to epithelial sinus mucosa cells of patients with chronic rhinosinusitis without nasal polyps (CRSsNP). Methods. IL-25, IL-33, and TSLP were measured by ELISA in the supernatant of cell cultures derived by CRSwNP (9 patients, 6 atopic) and CRSsNP (7 patients, 2 atopic) in baseline condition and following stimulation with Dermatophagoides pteronyssinus (DP), Aspergillus fumigatus (AF), and poly(I:C). Results. CRSwNP epithelial cells released increased levels of IL-25 (from 0.12 ± 0.06 pg/ml to 0.27 ± 0.1 pg/ml, p < 0.01) and TSLP (from 0.77 ± 0.5 pg/ml to 2.53 ± 1.17 pg/ml, p < 0.001) following poly(I:C) stimulation, while CRSsNP epithelial cells released increased levels of IL-25 and IL-33 following AF and DP stimulation, respectively (IL-25: from 0.18 ± 0.07 pg/ml to 0.51 ± 0.1 pg/ml, p < 0.001; IL-33: from 2.57 ± 1.3 pg/ml to 5.7 ± 3.1 pg/ml, p < 0.001). Conclusions. CRSwNP epithelial cells release TSLP and IL-25 when stimulated by poly(I:C) but not by DP or AF, suggesting that viral infection may contribute to maintain and amplify the T2 immune response seen in CRSwNP.

Role of Taste Receptors as Sentinels of Innate Immunity in the Upper Airway

“…More recently, human SCCs have also been found to be the source of epithelial-derived cytokine, IL-25 [ 30 , 31 ]. Unlike hematopoietic cytokines, epithelial-derived cytokines, namely, IL-25, TSLP, and IL-33, are released when airway epithelium is exposed to allergens, fungi, and viral antigens ( Figure 2 ) [ 59 ]. These cytokines act on resident group-2 innate lymphoid cells which trigger an eosinophilic type-2 inflammatory cascade [ 60 ].…”

The role of bitter and sweet taste receptors in upper airway innate immunity: Recent advances and future directions

“…SCCs are the predominant source of epithelial IL-25 which stimulates local group-2 innate lymphoid cells (ILC-2s). 31 , 52 Activated ILC-2s initiate a localized type 2 inflammatory response which includes massive secretion of the cytokine IL-13, which in a feed-forward loop induces SCC proliferation. 30 , 31 To that end, SCCs are present in greater number in inflamed versus non-inflamed tissue, inducing higher levels of IL-25 production in a manner that is increased in the presence of IL-13 and decreased with steroid exposure.…”

Lactobacilli Have a Niche in the Human Nose

“…The p value was corrected for multiple comparisons using the Holm-Sidak's multiple comparisons test (D, F, and G). See also Table S2. and CRS patients with nasal polyps (CRSwNP) (n = 6) were included, because we rationalized that adhesion to diseased or unstable epithelium could be different due to, for instance, the expression of different receptors (Boita et al, 2016). In Calu-3 cells, adhesion of L. casei AMBR2 was significantly higher (11.3% ± 3.2%) compared with L. rhamnosus GG (5.7% ± 2.7%; p < 0.0001), L. rhamnosus AMBR1 (2.6% ± 1%; p < 0.0001), and L. rhamnosus AMBR4 (6% ± 1.4%; p < 0.001) (Figure 3D).…”