Distribution And Function Of Different Subtypes Of Macrophages In Chronic Rhinosinusitis With Nasal Polyps

?Background? Chronic rhinosinusitis with nasal polyps(CRSw NP)is a multifactorial disorder characterized by exaggerated local immune responses.Tumor necrosis factor-?–induced protein 8–like 2(TIPE2)is a novel protein with potential immune modulating function.The expression and function of TIPE2 in human airway diseases are unclear.?Methods? The expression of TIPE2 in sinonasal mucosal samples was assessed by means of quantitative reverse transcript-polymerse chain reaction,immunohistochemistry,and Western blotting.The human monocytic/macrophage cell line,THP-1 cells,was stimulated with various cytokines.Computed tomography(CT)scan images,endoscopic findings,and symptoms were scored.?Results? Compared with non-eosinophilic polyps and control mucosa,the m RNA and protein expression of TIPE2 was significantly upregulated in eosinophilic polyps,with a further increase in those with asthma.TIPE2 was mainly expressed by M2 macrophages in sinonasal mucosa and its expression was upregulated in M2 macrophages in eosinophilic polyps.The number of CD68+CD163+ alternatively activated(M2)macrophages was increased in eosinophilic polyps.Interleukin(IL)-4 and IL-13,but not interferon(IFN)-? or IL-17 A,induced TIPE2 expression in differentiated THP-1 cells.The m RNA levels of IL-4 and IL-13 correlated with the m RNA levels of TIPE2 and M2 macrophage markers in sinonasal mucosa.Importantly,the number of TIPE2+ cells,particularly TIPE2+CD163+CD68+ M2 macrophages,correlated positively with the number of eosinophils and total inflammatory cells in sinonasal mucosa,as well as disease duration,CT scores,hyposmia scores,and polyp size in CRSw NP.?Conclusion? The T-helper 2 milieu is able to induce TIPE2 expression in macrophages.TIPE2-positive M2 macrophages potentially contribute to eosinophilic inflammation and disease progression in CRSw NP.Background: M2 macrophages are characterized by high IL-10 expression and are critical for resolving inflammation.Although increased accumulation of M2 macrophages has been demonstrated in chronic rhinosinusitis with nasal polyps(CRSw NP),particularly the eosinophilic type,their functional relevance in CRSw NP remains poorly understood.Methods: M1 and M2 macrophages and IL-10 expression in sinonasal tissues were detected by double immunofluorescence staining.THP-1 cells,a human monocytic leukemia cell line,were stimulated with various cytokines to study macrophage polarization and IL-10 expression.Polyp size,computed tomography(CT)scans,and symptom severity were scored.Results: Compared with numbers in control tissues,the numbers of total CD68+ macrophages,interferon regulatory factor 5 positive and CD68+ M1 macrophages,and CD163+CD68+ and CD206+CD68+ M2 macrophages were increased in both eosinophilic and non-eosinophilic polyps.However,compared with non-eosinophilic polyps,eosinophilic polyps contained fewer M1 macrophages and more M2 macrophages.Consistent with this,the M1/M2 macrophage ratio was increased in non-eosinophilic polyps,whereas it decreased in eosinophilic polyps.Strikingly,the number of IL-10+CD68+ macrophages and the percentage of IL-10+CD68+ macrophages relative to the total number of macrophages were decreased in eosinophilic polyps despite the upregulation of M2 macrophages in this type of polyp.The number of IL-10+CD68+ M2 macrophages negatively correlated with total symptoms scores,polyp sizes,total CT scores,and the total number of inflammatory cells in patients with eosinophilic CRSw NP.Poly I:C downregulated IL-10 expression in M2 macrophages differentiated from THP-1 cells in vitro.Conclusion: Impaired IL-10 production by M2 macrophages may contribute to sustained inflammation in eosinophilic CRSw NP.