Local amplifiers of IL-4Ralpha-mediated macrophage activation promote repair in lung and liver
IL-4 drives production of local tissue-specific factors (SP-A and C1q)
and expression of their receptor (Myo18A) on the macrophage surface for
full activation of tissue repair programs. These findings reveal the
existence within distinct tissues of an amplification system needed for
limiting tissue injury and promoting repair.
Minutti CM, Jackson-Jones LH, Garcia-Fojeda B, Knipper JA, Sutherland TE, Logan N, Rinqvist E, Guillamat-Prats R, Ferenbach DA, Artigas A, Stamme C, Chroneos ZC, Zaiss DM, Casals C, Allen JE.
Science 2017 Jun; 356: 1076.
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.
PubMed: 28495878. Doi: 10.1126/science.aaj2067.
