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

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 in...

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Detalles Bibliográficos
Autores: Minutti, Carlos, Jackson-Jones, Lucy, García-Fojeda García-Valdecasas, María Belén, Knipper, Johanna, Sutherland, Tara, Logan, Nicola, Ringqvist, Emma, Guillamat-Prats, Raquel, Ferenbach, David, Artigas, Antonio, Stamme, Cordula, Chroneos, Zissis, Zaiss, Dietmar, Casals Carro, María Cristina, Allen, Judith
Tipo de recurso: artículo
Fecha de publicación:2017
País:España
Institución:Universidad Complutense de Madrid (UCM)
Repositorio:Docta Complutense
Idioma:inglés
OAI Identifier:oai:docta.ucm.es:20.500.14352/94512
Acceso en línea:https://hdl.handle.net/20.500.14352/94512
Access Level:acceso abierto
Palabra clave:577.1
612.017
Tissue repair
Macrophages
Surfactant protein A
C1q
Interleukin-4
Type 2 immune response
Alternative activation
Defense collagens
Proliferation
Bioquímica (Biología)
Inmunología
2412 Inmunología
2403 Bioquímica
Descripción
Sumario: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.