Abstract
Type I interferon (IFN-I, including IFN-α and IFN-β) response has been implicated in eosinophilic inflammation, in addition to antiviral function. This study aimed to investigate the role of IFN-I in the pathogenesis of eosinophilic chronic rhinosinusitis (ECRS). IFN-α, IFN-β, cytokine expression, and IFN-β cellular localization in the sinonasal tissue from control subjects and ECRS patients with nasal polyps (NP) were determined using real time-PCR, ELISA, and immunohistochemistry. ECRS was induced in wild-type (WT) and IFNAR1 knockout (Ifnar1−/−) mice by intranasal challenge with Aspergillus protease and ovalbumin. Stromal cells cultured from NP tissue were stimulated by exogenous IFN-β, and their CCL11 production and IRF3, IRF7, STAT1, STAT2, and IRF9 gene and/or protein expression were measured. IFN-β, IL-5, IL-13, and CCL11 expression was higher in the NP tissue from ECRS patients, compared to the control group. IFN-β was highly colocalized with the CD11c+ cells in NP. IFN-β levels positively correlated with IL-5, IL-13, and CCL11 levels as well as the number of eosinophils in the NP tissue and CT score. The histological severity of ECRS, levels of IL-4, IL-5, IL-13, and CCL11 in the nasal lavage fluid, and total serum IgE levels were less in Ifnar1−/− mice than in WT mice. CCL11 production, and STAT1 and STAT2 mRNA and STAT1, phospho-STAT1, and phospho-STAT2 protein expression were significantly increased by exogenous IFN-β in NP stromal cells. Our data suggest that IFN-β response was upregulated in ECRS and may play role in ECRS development. IFN-β may contribute to ECRS by enhancing CCL11 production. Thus, increased IFN-β response in the sinonasal mucosa may underlie ECRS pathogenesis.
Highlights
Eosinophilic chronic rhinosinusitis (ECRS) is an inflammatory disease characterized by remarkable infiltration of eosinophils and elevated type 2 response, and is frequently associated with nasal polyp (NP) tissue [1]
We compared the expression of IFN-I (IFN-α and IFN-β) from sinonasal tissues to evaluate whether IFN-I expression in the NP tissue from the ECRS group differs from that in the NP tissue from non-ECRS group and the uncinate process mucosa from the control group
IFN-β+ cells were mainly localized in the lamina propria and significantly increased in the eosinophilic NP tissues compared with the control and non-eosinophilic groups (P < 0.001; Figure 1F)
Summary
Eosinophilic chronic rhinosinusitis (ECRS) is an inflammatory disease characterized by remarkable infiltration of eosinophils and elevated type 2 response, and is frequently associated with nasal polyp (NP) tissue [1]. IFN-I potently modulate both innate and adaptive immune responses, promoting antigen presentation, natural killer cell functions, and development of effector T and B cell responses, while controlling pro-inflammatory pathways and production of other cytokines [5, 6]. Zhang et al showed a potential association between IFN-I and type 2 immune response-skewed eosinophilic inflammation in patients with CRS [13]. They could not clearly explain the role of IFN-I response in ECRS
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