Minutti, Carlos M and Jackson-Jones, Lucy H and García-Fojeda, Belén and Knipper, Johanna A and Sutherland, Tara E and Logan, Nicola and Ringqvist, Emma and Guillamat-Prats, Raquel and Ferenbach, David A and Artigas, Antonio and Stamme, Cordula and Chroneos, Zissis C and Zaiss, Dietmar M and Casals, Cristina and Allen, Judith E (2017) Local amplifiers of IL-4Rα-mediated macrophage activation promote repair in lung and liver. Science, 356 (6342). pp. 1076-1080. ISSN 0036-8075
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Abstract
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.