Altered Th17/Treg Ratio In Nasal Polyps: Association With Patterns Of Inflammation And Mucosal Remodeling

Background: Chronic rhinosinusitis with nasal polyps(CRSw NP) is a heterogeneous disease that can be classified as eosinophilic or non-eosinophilic. Nasal polyps can exhibit different types of mucosal inflammation and responses to treatment. Imbalanced ratios of T-helper 17(Th17) and regulatory T(Treg) cells may contribute to the pathogenesis of nasal polyps.Objective: This study assessed the frequency of Th17 and Treg cells in patients with nasal polyps and tested for associations with mucosal remodeling.Methods: Surgical samples from 12 controls and 33 CRSw NP patients were analyzed histopathologically. The frequency of Th17 and Treg cells in peripheral blood mononuclear cells(PBMCs) and tissues were determined using flow cytometry.Results:(1)Eosinophilic CRSw NP(ECRSw NP) patients exhibited robust eosinophilia, whereas noneosinophilic CRSw NP(non-ECRSw NP) patients were characterized by neutrophilia.(2) Compared with controls, the thickness of the submucosal basement membrane(SBM) in both ECRSw NP and non-ECRSw NP was significantly increased(P<0.001 for both). Moreover, ECRSw NP presented with higher thickness of SBM compared with non-ECRSw NP(P<0.001).Compared with controls, the thickness of the collagen within the basement membrane(CBM) in both ECRSw NP and non-ECRSw NP was significantly increased(P<0.001 for both). Besides, non-ECRSw NP presented with higher thickness of CBM compared with ECRSw NP(P<0.001).Compared with controls, the mean rank of subepithelial collagen deposition(SCD)in both ECRSw NP and non-ECRSw NP was significantly higher(P<0.001 for both). Besides, non-ECRSw NP exhibited a higher mean rank of SCD compared with ECRSw NP(P<0.05).Compared with controls, the mean rank of edemain both ECRSw NP and non-ECRSw NP was significantly higher(P<0.001,P<0.05). Besides, ECRSw NP preseted with a higher mean rank of edema compared with non-ECRSw NP(P<0.05).(3)Compared with controls, the proportion of Th17 cells in PBMCs and tissues in ECRSw NP and non-ECRSw NP was significantly increased(P<0.001 for both). Besides, non-ECRSw NP preseted with a higher proportion of Th17 cells compared with ECRSw NP(P<0.001).Compared with controls, the proportion of Treg cells in PBMCs and tissues in ECRSw NP and non-ECRSw NP was significantly decreased(P<0.001 for both). What’s more, ECRSw NP exhibited a lower proportion of Treg cells compared with non-ECRSw NP(P<0.05).Compared with controls, the ratio of Th17/Treg cells both in PBMCs in ECRSw NP and non-ECRSw NP was significantly increased(P<0.05 and P<0.001) and the the ratio of Th17/Treg cells both in tissues in ECRSw NP and non-ECRSw NP was significantly increased(P<0.001 for both). Besides, non-ECRSw NP presented with a higherratio of Th17/Treg cells both in PBMCs and tissues compared with non-ECRSw NP(P<0.05 for both).(4) Spearman’s correlation analysisshowed that the frequency of Th17 cells waspositively correlatedwith the number of eosinophils(EOS; r=0.425, P<0.01)and neutrophils(NEU; r=0.628, P<0.01), the thickness of CBM(r=0.564,P<0.05) and SBM(r=0.534, P<0.01), the degree of SCD(r=0.572, P<0.05), and edema(r=0.401, P<0.05).By contrast, the frequency of Treg cells was negativelycorrelated with the number of EOS(r= –0.626, P<0.05)and NEU(r= –0.375, P<0.05), the thickness of the SBM(r= –0.472, P<0.05), and the degree of edema(r= –0.625,P<0.01). Moreover, the ratio of Th17/Treg cells was positivelycorrelated with the number of EOS(r=0.481, P<0.05) and NEU(r=0.641, P<0.01), the thickness of the CBM(r=0.453,P<0.01), and the degree of SCD(r=0.427, P<0.05). We did not find a gramatic correlation between the ratio of Th17/Treg and the thickness of the SBM(r=0.437, P =0.054), or the degree of edema(r= 0.322,P=0.061).Conclusion: Th17/Treg cell imbalance in nasal polyps(both in tissues and PBMCs) may contribute to different inflammatory patterns(eosinophilic versus neutrophilic inflammation) and corresponding features of mucosal remodeling. Effective strategies can be designed to target a Th17/Treg imbalance to restore immune homeostasis in nasal polyps.