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

Research output: Contribution to journalArticle

  • External authors:
  • Carlos M Minutti
  • Lucy H Jackson-Jones
  • Belen Garcia-Fojeda
  • Johanna A Knipper
  • Nicola Logan
  • Emma Rinqvist
  • Raquel Guillamat-Prats
  • David A Ferenbach
  • Antonio Artigas
  • Cordula Stamme
  • Zissis C Chroneos
  • Dietmar M Zaiss
  • Cristina Casals

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 IL-4-dependent macrophage proliferation and activation, accelerating parasite clearance and reducing pulmonary injury following infection with a lung-migrating helminth. In the peritoneal cavity and liver, C1q enhancement of type 2 macrophage activation was required for liver repair following bacterial infection, but resulted in fibrosis following 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.

Bibliographical metadata

Original languageEnglish
JournalScience
Volume356
Early online date11 May 2017
DOIs
StatePublished - 2017