Abstract
BackgroundInterleukin(IL)-25, IL-33, and thymic stromal lymphopoietin (TSLP) underlie the crosstalk between epithelial cells and dendritic cells (DCs) during the development of Th2 responses. This study aimed to measure the expressions of IL-17RB, ST2 and TSLPR, receptor of IL-25, IL-33, and TSLP respectively, on myeloid DCs in nasal polyps (NP) and evaluate their association with local Th2 inflammation and disease severity in patients with NP.MethodsSamples were collected from 30 NP patients and 16 control subjects recruited prospectively. The mRNA expression of cytokines, including TSLP, IL-25 and IL-33, as well as interferon (IFN)-γ, IL-4, IL-5, IL-13 and IL-17A in NP and control tissues was examined by qualitative polymerase chain reaction (qPCR). The expression of IL-17RB, ST2 and TSLPR as well as other surface markers on myeloid DCs (mDCs) was examined by flow cytometry.ResultsIncreased numbers of total and activated mDCs were found in NP patients. mDCs demonstrated significantly higher expression of IL-17RB, ST2 and TSLPR than those in control tissues. The activated mDCs exhibited up-regulations of OX40L and ICOSL, but down-regulation of PDL1 in NP. Moreover, the IL-17RB, ST2 and TSLPR levels on mDCs were positively correlated with IL-25, IL-33 and TSLP mRNA levels, respectively, in NP. Furthermore, IL-17RB and ST2 expressions on mDCs were correlated with the IL-5 mRNA level as well as eosinophil number in NP. Importantly, the IL-17RB expression on mDCs and the OX40L expression on activated mDCs in NP were positively correlated with CT score and total nasal symptom score.ConclusionsIncreased expressions of IL-17RB and ST2 on mDCs are associated with enhanced local Th2 inflammation in NP, suggesting that mDCs might play a role in IL-25- and IL-33-induced type 2 responses and eosinophilic inflammation in NP.
Highlights
Chronic rhinosinusitis (CRS), affecting 14% of adults in the United States and 8% in China [1, 2], is a chronic mucosal inflammation mediated by innate and adaptive immune cells and mediators in nasal sinus
In nasal polyps (NP), it has been reported that myeloid DCs (mDCs) are increased in NP tissues [15, 16], and two distinct dendritic cells (DCs) subsets, OX40 ligand (OX40L)/PDL1+ DCs with Th2-cell-priming ability and low OX40L/PDL1-expressing DCs with Th1/17-cellinducing ability, are associated with forming eosinophilic and non-eosinophilic endotype of NP respectively [17], indicating an important role DCs play in the modulation of T cell response in NP
For the other functional markers on DC surface, we found that OX40L expression on C D86+CD1c+ DCs was positively correlated with IL-25 and IL-4 mRNA expression (r = 0.394 and 0.416) (Fig. 5b, j), but not with IL-33 or thymic stromal lymphopoietin (TSLP) (Additional file 1: Table S3)
Summary
Chronic rhinosinusitis (CRS), affecting 14% of adults in the United States and 8% in China [1, 2], is a chronic mucosal inflammation mediated by innate and adaptive immune cells and mediators in nasal sinus. In NP, it has been reported that mDCs are increased in NP tissues [15, 16], and two distinct DC subsets, OX40L/PDL1+ DCs with Th2-cell-priming ability and low OX40L/PDL1-expressing DCs with Th1/17-cellinducing ability, are associated with forming eosinophilic and non-eosinophilic endotype of NP respectively [17], indicating an important role DCs play in the modulation of T cell response in NP. This study aimed to measure the expressions of IL-17RB, ST2 and TSLPR, receptor of IL-25, IL-33, and TSLP respectively, on myeloid DCs in nasal polyps (NP) and evaluate their association with local Th2 inflammation and disease severity in patients with NP
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