RT Journal Article
T1 Local amplifiers of IL-4Rα–mediated macrophage activation promote repair in lung and liver
A1 Minutti, Carlos
A1 Jackson-Jones, Lucy
A1 García-Fojeda García-Valdecasas, María Belén
A1 Knipper, Johanna
A1 Sutherland, Tara
A1 Logan, Nicola
A1 Ringqvist, Emma
A1 Guillamat-Prats, Raquel
A1 Ferenbach, David
A1 Artigas, Antonio
A1 Stamme, Cordula
A1 Chroneos, Zissis
A1 Zaiss, Dietmar
A1 Casals Carro, María Cristina
A1 Allen, Judith
AB 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.
AB Local macrophage clean-up.Infection, especially by helminths or bacteria, can cause tissue damage (see the Perspective by Bouchery and Harris). Minutti et al. studied mouse models of helminth infection and fibrosis. They expressed surfactant protein A (a member of the complement component C1q family) in the lung, which enhanced interleukin-4 (IL-4)-mediated proliferation and activation of alveolar macrophages. This activation accelerated helminth clearance and reduced lung injury. In the peritoneum, C1q boosted macrophage activation for liver repair after bacterial infection. By a different approach, Bosurgi et al. discovered that after wounding caused by migrating helminths in the lung or during inflammation in the gut of mice, IL-4 and IL-13 act only in the presence of apoptotic cells to promote tissue repair by local macrophages. Science, this issue p.1076, p.1072; see also p.1014
PB American Association for the Advancement of Science
SN 0036-8075
YR 2017
FD 2017
LK https://hdl.handle.net/20.500.14352/94512
UL https://hdl.handle.net/20.500.14352/94512
LA eng
NO Carlos M. Minutti et al. ,Local amplifiers of IL-4Rα–mediated macrophage activation promote repair in lung and liver.Science356,1076-1080(2017).DOI:10.1126/science.aaj2067
NO Ministerio de Economía y Competitividad (España)
NO Instituto de Salud Carlos III
NO Medical Research Council UK
NO European Commission
NO National Institutes of Health U.S.A.
NO German Research Council
DS Docta Complutense
RD 11 ago 2024