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Science. 2017 Jun 9;356(6342):1072-1076. doi: 10.1126/science.aai8132. Epub 2017 May 11.

Macrophage function in tissue repair and remodeling requires IL-4 or IL-13 with apoptotic cells.

Author information

1
Department of Immunobiology, School of Medicine, Yale University, New Haven, CT 06520, USA.
2
Department of Molecular Biophysics and Biochemistry, W. M. Keck Foundation Biotechnology Resource Laboratory, School of Medicine, Yale University, New Haven, CT 06520, USA.
3
Instituto de Farmacología, Facultad de Medicina, Universidad de Buenos Aires, Ciudad Autónoma de Buenos Aires, Argentina.
4
I. Department of Medicine and Department of General, Visceral and Thoracic Surgery, University Medical Center Hamburg-Eppendorf, Hamburg 20246, Germany.
5
Department of Internal Medicine (Rheumatology), School of Medicine, Yale University, New Haven, CT 06520, USA.
6
Howard Hughes Medical Institute, School of Medicine, Yale University, New Haven, CT 06520, USA.
7
Department of Neurology, School of Medicine, Yale University, New Haven, CT 06520, USA. sourav.ghosh@yale.edu carla.rothlin@yale.edu.
8
Department of Pharmacology, School of Medicine, Yale University, New Haven, CT 06520, USA.
9
Department of Immunobiology, School of Medicine, Yale University, New Haven, CT 06520, USA. sourav.ghosh@yale.edu carla.rothlin@yale.edu.

Abstract

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.

PMID:
28495875
PMCID:
PMC5556699
DOI:
10.1126/science.aai8132
[Indexed for MEDLINE]
Free PMC Article

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