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Minutti, Carlos M.; Jackson-Jones, Lucy H.; García-Fojeda, Belén; Knipper, Johanna A.; Sutherland, Tara E.; Logan, Nicola; Rinqvist, Emma; Guillamat-Prats, Raquel; Ferenbach, David A.; Artigas, Antonio; Stamme, Cordula; Chroneos, Zissis C.; Zaiss, Dietmar M.; Casals, Cristina; Allen, Judith E.
Science, 06/2017, Volume: 356, Issue: 6342Journal Article
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.
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