Macrophage polarization into M1 (classically activated) versus M2 (alternatively activated) phenotype is orchestrated by distinct cytokine signals. Which cytokine signature drives M2 polarization and is associated with tissue repair and fibrosis?

• A IFN-γ and LPS (TLR4 ligand) signaling through STAT1 pathway
• B TNF-α and IL-12 signaling through NF-κB and STAT4
• C IL-17 and IL-23 signaling through Act1-TRAF6 pathway
• D IL-4 and IL-13 signaling through JAK1/STAT6 pathway ✓

Explanation

M2 macrophage polarization (alternatively activated, anti-inflammatory, pro-repair phenotype) is driven primarily by IL-4 and IL-13, both of which signal through JAK1 (and JAK3 for IL-4) and STAT6 phosphorylation. M2 macrophages express arginase-1 (metabolizing arginine to ornithine/polyamines/proline, promoting collagen synthesis), mannose receptor (CD206), Ym1/2, TGF-β, and IL-10. They suppress inflammation, promote tissue repair, and drive fibrosis. M1 polarization is driven by IFN-γ/LPS via STAT1 and NF-κB, producing NO, TNF, IL-12, and IL-6. IL-17/IL-23 drives neutrophil recruitment and Th17 responses; TNF/IL-12 contributes to M1 activation, not M2.

Reference: Robbins & Cotran Pathologic Basis of Disease, 10th ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

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