TY - JOUR
T1 - Local amplifiers of IL-4Rα-mediated macrophage activation promote repair in lung and liver
AU - Minutti, Carlos M
AU - Jackson-Jones, Lucy H
AU - Garcia-Fojeda, Belen
AU - Knipper, Johanna A
AU - Sutherland, Tara
AU - Logan, Nicola
AU - Rinqvist, Emma
AU - Guillamat-Prats, Raquel
AU - Ferenbach, David A
AU - Artigas, Antonio
AU - Stamme, Cordula
AU - Chroneos, Zissis C
AU - Zaiss, Dietmar M
AU - Casals, Cristina
AU - Allen, Judith
PY - 2017/5/11
Y1 - 2017/5/11
N2 - 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.
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 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.
U2 - 10.1126/science.aaj2067
DO - 10.1126/science.aaj2067
M3 - Article
VL - 356
SP - 1076
EP - 1080
JO - Science
JF - Science
SN - 0036-8075
IS - 6342
ER -