Responses of Nasal Polyp-Derived Macrophages to Inflammatory Cues and Potential Pathological Roles in Type 2 Chronic

Hyunkyung Cha1, Ara Jo2, Hee-Suk Lim2

  • 1Department of Otorhinolaryngology-Head and Neck Surgery, Soonchunhyang University Cheonan Hospital, Soonchunhyang University College of Medicine, Cheonan, Korea.

Abstract

Insights

Macrophages in nasal polyps (NP) play a key role in chronic rhinosinusitis with nasal polyps (CRSwNP). Type 2 CRSwNP shows elevated TSLP and OSM from macrophages, suggesting a role in disease.

Area of Science:

  • Immunology
  • Pathophysiology
  • Molecular Biology

Background:

  • Macrophages are crucial in nasal polyp (NP) pathogenesis, but their heterogeneity and role in different chronic rhinosinusitis with nasal polyps (CRSwNP) endotypes remain unclear.
  • Understanding macrophage behavior is vital for targeted therapies in CRSwNP.

Purpose of the Study:

  • To investigate the distribution and inflammatory responses of macrophages derived from nasal polyps (NP) in relation to CRSwNP endotypes.
  • To elucidate the specific roles of macrophage subsets and their cytokine production in Type 2 (T2) CRSwNP.

Main Methods:

  • Analysis of macrophage subset distribution in NP using bulk RNA sequencing and CIBERSORTx.
  • Evaluation of cytokine and chemokine production by NP-derived macrophages upon stimulation with IL-4, SEB, and LPS.
  • Immunofluorescence staining of NP tissues to validate findings.

Main Results:

  • Type 2 (T2) CRSwNP demonstrated a higher proportion of M2 macrophages compared to non-type 2 (NT2) CRSwNP.
  • NP-derived macrophages showed increased baseline TSLP levels in CRSwNP patients.
  • TSLP and OSM expression were significantly upregulated in T2 CRSwNP macrophages upon IL-4 or SEB stimulation, with higher TSLP/OSM-expressing cells in T2 NP tissues.

Conclusions:

  • Macrophages in T2 CRSwNP exhibit distinct responses, with elevated TSLP and OSM expression.
  • These findings suggest that NP-derived macrophages, particularly in T2 CRSwNP, contribute to the disease's pathophysiology through specific cytokine profiles.

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