Macrophage function in tissue repair and remodeling requires IL-4/IL-13 with apoptotic cells [Run1]

Tissue repair is a subset of a broad repertoire of IL-4/IL-13-dependent host responses during helminth infections. Here, we show that IL-4/IL-13 alone were not sufficient, but IL-4/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 induction of anti-inflammatory/tissue repair genes in the lung following helminth infection or the damage caused by induction of colitis in the gut. In contrast, 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/IL-13. Overall design: RNA sequencing of lung resident macrophages from WT and Axl-/-Mertk-/- mice upon infection with N. brasiliensis

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Bosurgi L, Cao YG, Cabeza-Cabrerizo M, Tucci A, Hughes LD, Kong Y, Weinstein JS, Licona-Limon P, Schmid ET, Pelorosso F, Gagliani N, Craft JE, Flavell RA, Ghosh S, Rothlin CV