Increased Expression of TIPE2 in Alternatively Activated Macrophages Is Associated with Chronic Rhinosinusitis with Nasal Polyps

Chronic rhinosinusitis with nasal polyps (CRSwNP) is a multifactorial disease of unknown cause. Tumor necrosis factor-α-induced protein 8-like 2 (TIPE2) is a novel multifunctional protein with immunomodulatory effects. We sought to investigate the expression and distribution of TIPE2 in sinonasal mucosa, and to evaluate its association with local inflammation and disease severity in CRSwNP. The expression of TIPE2 in sinonasal mucosa was assessed by means of quantitative RT-PCR and immunohistochemistry. Local inflammatory cells were counted. Clinical symptom severity was scored. T cells related cytokines were detected using RT-PCR. Vitro culture was used to elucidate the effect of cytokines on TIPE2 expression. Compared with controls, the expression of TIPE2 were significantly increased in sinonasal mucosa of both eosinophilic and non-eosinophilic CRSwNP with a further increase in eosinophilic CRSwNP. TIPE2 was predominantly expressed in CD68+ macrophages, especially in CD68+CD163+ alternatively activated (M2) macrophages, and in some CD11c+ dendritic cells in eosinophilic CRSwNP. In addition, TIPE2 expression was upregulated by IL-4 and IL-13, whereas inhibited by IL-10 and LPS in THP-1 cells. The levels of IL-4 and IL-13 positively correlated with the levels of TIPE2 in sinonasal mucosa. More importantly, the numbers of TIPE2+CD163+CD68+M2 macrophages significantly positively correlated with eosinophil and total inflammatory cell counts in sinonasal mucosa, duration of disease, total computer tomography scan scores, olfaction loss, and nasal polyp size in CRSwNP. IL-4 and IL-13 induced overexpression of TIPE2 in M2 macrophages could potentially contribute to the persistence of CRSwNP, especially of eosinophilic CRSwNP.