IL-23-induced macrophage polarization and its pathological roles in mice with imiquimod-induced psoriasis

Area of Science:

• Immunology
• Cell Biology
• Dermatology

Background:

• Macrophages are key immune cells with diverse phenotypes, broadly classified as M1 (inflammatory) and M2 (anti-inflammatory).
• Distinct macrophage subsets play critical roles in tissue homeostasis, inflammation, and disease pathogenesis.
• Understanding macrophage polarization is crucial for developing targeted therapies for inflammatory conditions.

Purpose of the Study:

• To identify and characterize a novel pathogenic macrophage subpopulation induced by Interleukin-23 (IL-23).
• To elucidate the molecular mechanisms underlying IL-23-driven macrophage polarization and cytokine production.
• To investigate the role of IL-23-induced macrophages in the pathogenesis of psoriasis.

Main Methods:

• Primary mouse peritoneal macrophages were stimulated in vitro with cytokines.
• Gene expression profiling, real-time PCR, ELISA, and flow cytometry were used to detect cytokine and chemokine expression.
• Adoptive transfer experiments and imiquimod-induced psoriasis mouse models were employed to assess in vivo function.

Main Results:

• IL-23 stimulation induced a unique macrophage subset distinct from M1 and M2 phenotypes.
• These IL-23-treated macrophages produced significant amounts of IL-17A, IL-22, and IFN-γ.
• IL-23 induced IL-17A via the STAT3-RORγT pathway and IFN-γ via T-bet.
• IL-23-induced macrophages exacerbated dermatitis in a psoriasis-like mouse model.

Conclusions:

• A novel pathogenic macrophage subpopulation is driven by IL-23, characterized by a distinct gene expression profile.
• IL-23-induced macrophages contribute significantly to Th17-cytokine-related pathogenesis, such as in psoriasis.
• This finding offers new insights into macrophage plasticity and its role in inflammatory diseases.