Local amplifiers of IL-4Rα–mediated macrophage activation promote repair in lung and liver

• Autores: Carlos M. Minutti, Lucy H. Jackson‐Jones, Belen García-Fojeda García-Valdecasas
• Localización: Science, ISSN 0036-8075, Vol. 356, Nº 6342, 2017, págs. 1076-1080
• Idioma: inglés
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• Resumen

  • The type 2 immune response controls helminth infection and maintains tissue homeostasis but can lead to allergy and fibrosis if not adequately regulated. We have discovered local tissue-specific amplifiers of type 2–mediated macrophage activation. In the lung, surfactant protein A (SP-A) enhanced interleukin-4 (IL-4)–dependent macrophage proliferation and activation, accelerating parasite clearance and reducing pulmonary injury after infection with a lung-migrating helminth. In the peritoneal cavity and liver, C1q enhancement of type 2 macrophage activation was required for liver repair after bacterial infection, but resulted in fibrosis after peritoneal dialysis. IL-4 drives production of these structurally related defense collagens, SP-A and C1q, and the expression of their receptor, myosin 18A. These findings reveal the existence within different tissues of an amplification system needed for local type 2 responses.