Type 2–mediated activation of macrophages is required for tissue defense and homeostasis. In Science, Minutti et al. show that local amplifiers enhance interleukin 4 (IL-4)-dependent activation and proliferation of macrophages in a tissue-specific manner. Sp-A, the main component of pulmonary surfactant, enhances the IL-4-induced proliferation of alveolar macrophages, and Sp-A-deficient mice infected with Nippostrongylus brasiliensis have less proliferation of alveolar macrophages, worm clearance and tissue healing than that of wild-type mice. C1q, a soluble defense collagen related to Sp-A, enhances the IL-4-induced proliferation of peritoneal macrophages, and C1q-deficient mice have less type 2 macrophage–dependent fibrosis after peritoneal dialysis and less liver repair after infection with Listeria monocytogenes than wild-type mice. Both proteins are induced by IL-4, trigger the cell-surface localization of and signal through the unconventional myosin Myo18A but show alveolar or peritoneal macrophage specificity. Such specificity might depend on the expression of co-receptors for Myo18A.
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Visan, I. Tissue-specific amplifiers. Nat Immunol 18, 715 (2017). https://doi.org/10.1038/ni.3784