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Bosurgi, Lidia; Cao, Y. Grace; Cabeza-Cabrerizo, Mar; Tucci, Andrea; Hughes, Lindsey D; Kong, Yong; Weinstein, Jason S; Licona-Limon, Paula; Schmid, Edward T; Pelorosso, Facundo; Gagliani, Nicola; Craft, Joseph E; Flavell, Richard A; Ghosh, Sourav; Rothlin, Carla V (2017)

MACROPHAGE FUNCTION IN TISSUE REPAIR AND REMODELING REQUIRES IL-4 OR IL-13 WITH APOPTOTIC CELLS

Science 356(SI):1072-+
full text

Tissue repair is a subset of a broad repertoire of interleukin-4 (IL-4)- and IL-13-dependent host responses during helminth infection. Here we show that IL-4 or IL-13 alone was not sufficient, but IL-4 or IL-13 together with apoptotic cells induced the tissue repair program in macrophages. Genetic ablation of sensors of apoptotic cells impaired the proliferation of tissue-resident macrophages and the induction of anti-inflammatory and tissue repair genes in the lungs after helminth infection or in the gut after induction of colitis. By contrast, the recognition of apoptotic cells was dispensable for cytokine-dependent induction of pattern recognition receptor, cell adhesion, or chemotaxis genes in macrophages. Detection of apoptotic cells can therefore spatially compartmentalize or prevent premature or ectopic activity of pleiotropic, soluble cytokines such as IL-4 or IL-13.