Abstract

Background: Recent studies have implied a role for Th17 cells in CRS with nasal polyps (CRSwNP) patients. However, the capacity of these cells to produce Th17 cytokines is still unknown. Here we sought to quantify IL-17A, IL-17F, IL-21, and IL-22 cytokines produced by Th17 cells in mucosal tissue and peripheral blood of CRSwNP, CRS without nasal polyps (CRSsNP) and control patients.Methods: Samples were prospectively collected from CRS patients and non-CRS controls. We used flow cytometry to characterize the Th17 cells and their cytokines in sinonasal tissue and peripheral blood.Results: A total of 36 patients were recruited to the study. CRSwNP patients had significantly more tissue IL-17A (9.53 ± 2.71 vs. 1.11 ± 0.43 vs. 0.77 ± 0.07), IL-17F (4.96 ± 1.48 vs. 0.88 ± 0.31 vs. 0.56 ± 0.04), IL-21 (5.55 ± 2.01 vs. 1.60 ± 0.71 vs. 1.53 ± 0.55) and IL-22 (4.73 ± 1.58 vs. 0.70 ± 0.28 vs. 0.88 ± 0.26) producing Th17 cells compared to CRSsNP and control mucosa per mg of tissue, respectively. Allergic CRSwNP patients had decreased numbers of IL-21 producing Th17 cells compared to non-Allergic CRSwNP. (1.69 ± 0.57 vs. 9.41 ± 3.23) per mg of tissue, respectively (Kruskal-Wallis p < 0.05).Conclusion: In summary our study identified increased numbers of IL-17A, IL-17F, IL-21 and IL-22 positive Th17 cells in CRSwNP patient polyps and peripheral blood suggesting an altered activation state of those cells both locally and systemically. Atopic CRSwNP had decreased amounts of tissue Th17 cell derived IL-21 implying a potential protective role for IL-21 in CRSwNP allergic inflammation.

Highlights

  • T helper 17 (Th17) cells are characterized by CC motif 6 chemokine receptor (CCR6) expression and produce the signature cytokines interleukin-17A (IL-17A), IL-17F, IL-21, and IL-22

  • Th17 Cells Are Increased in chronic rhinosinusitis (CRS) with nasal polyps (CRSwNP) Mucosa

  • CRSwNP patients had more Th17 cells in the polyps compared to CRSsNP and control mucosa (40.39 ± 7.75 vs. 16.19 ± 4.49 vs. 9.26 ± 4.32 per mg of tissue respectively, Kruskal-Wallis p < 0.01) (Figure 1B)

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Summary

Introduction

T helper 17 (Th17) cells are characterized by CC motif 6 chemokine receptor (CCR6) expression and produce the signature cytokines interleukin-17A (IL-17A), IL-17F, IL-21, and IL-22. Th17 cells play a significant role in the adaptive immune system by generating inflammation in response to infection, in particular to Candida albicans and Staphylococcus aureus (Brucklacher-Waldert et al, 2009). Both IL-17A and IL-17F cause the up-regulation of pro-inflammatory cytokines and chemokines such as IL-6, granulocyte colony-stimulating factor (GCSF), and CXCL1 and CXCL2. Recent studies have implied a role for Th17 cells in CRS with nasal polyps (CRSwNP) patients. We sought to quantify IL-17A, IL-17F , IL-21, and IL-22 cytokines produced by Th17 cells in mucosal tissue and peripheral blood of CRSwNP, CRS without nasal polyps (CRSsNP) and control patients

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