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

Carlos M. Minutti, Lucy H. Jackson-Jones, Belén García-Fojeda, Johanna A. Knipper, Tara E. Sutherland, Nicola Logan, Emma Rinqvist, Raquel Guillamat-Prats, David A. Ferenbach, Antonio Artigas, Cordula Stamme, Zissis C. Chroneos, Dietmar M. Zaiss, Cristina Casals, Judith E. Allen

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69 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)1076-1080
Number of pages5
JournalScience
Volume356
Issue number6342
DOIs
StatePublished - Jun 9 2017

All Science Journal Classification (ASJC) codes

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    Minutti, C. M., Jackson-Jones, L. H., García-Fojeda, B., Knipper, J. A., Sutherland, T. E., Logan, N., Rinqvist, E., Guillamat-Prats, R., Ferenbach, D. A., Artigas, A., Stamme, C., Chroneos, Z. C., Zaiss, D. M., Casals, C., & Allen, J. E. (2017). Local amplifiers of IL-4Ra-mediated macrophage activation promote repair in lung and liver. Science, 356(6342), 1076-1080. https://doi.org/10.1126/science.aaj2067