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  • Minutti 2017 AAM pure

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

Research output: Contribution to journalJournal article

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  • Carlos M Minutti
  • Lucy H Jackson-Jones
  • Belén García-Fojeda
  • Johanna A Knipper
  • Tara E Sutherland
  • Nicola Logan
  • Emma Ringqvist
  • 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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<mark>Journal publication date</mark>9/06/2017
<mark>Journal</mark>Science
Issue number6342
Volume356
Number of pages5
Pages (from-to)1076-1080
Publication StatusPublished
Early online date11/05/17
<mark>Original language</mark>English

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.