Responses of nasal polyp-derived macrophages to inflammatory cues and potential pathological roles in type 2 chronic rhinosinusitis with nasal polyps

Abstract

Objective.: The role of highly plastic and heterogeneous macrophages in the pathogenesis of nasal polyps (NP) is not well understood. We aimed to investigate the distribution and responses of NP-derived macrophages to inflammatory cues according to endotypes of chronic rhinosinusitis with nasal polyps (CRSwNP).

Methods.: The distribution of macrophage subsets was analyzed using NP bulk RNA sequencing data with CIBERSORTx program. The cytokines and chemokines produced by NP-derived macrophages following stimulation with interleukin-4 (IL-4), staphylococcal enterotoxin B (SEB), and lipopolysaccharide (LPS) were evaluated using a multiplex cytokine assay. Immunofluorescence staining in NP tissues was conducted to validate the findings.

Results.: Type 2 (T2) CRSwNP exhibited a significantly higher proportion of M2 macrophages, whereas both M1 and M2 macrophage populations were elevated in non-type 2 (NT2) CRSwNP. Baseline cytokine analysis of NP-derived macrophages revealed an increase in TSLP levels in CRSwNP compared to controls. Furthermore, TSLP expression was significantly upregulated from baseline levels following IL-4 or SEB stimulation in T2 CRSwNP. Notably, IL-4 stimulation led to an increase in OSM only in T2 CRSwNP. Additionally, the number and proportion of TSLP- and OSM-expressing cells among CD163-positive cells were significantly higher in the NP of T2 CRSwNP patients.

Conclusion.: NP-derived macrophages from T2 CRSwNP exhibit elevated expression of TSLP and OSM in response to IL-4 or SEB, potentially contributing to the pathophysiology of T2 CRSwNP.