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
Department of Immunobiology, School of Medicine, Yale University, New Haven, CT 06520, USA.
Department of Molecular Biophysics and Biochemistry, W. M. Keck Foundation Biotechnology Resource Laboratory, School of Medicine, Yale University, New Haven, CT 06520, USA.
Science. 2017 Jun 9;356(6342):1072-1076. doi: 10.1126/science.aai8132. Epub 2017 May 11.
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.
组织修复是蠕虫感染期间白细胞介素-4（IL-4）和白细胞介素-13依赖性宿主反应广泛组成部分中的一个子集。在此我们表明，单独的IL-4或IL-13并不足够，但IL-4或IL-13与凋亡细胞一起可诱导巨噬细胞中的组织修复程序。凋亡细胞传感器的基因消融损害了组织驻留巨噬细胞的增殖以及蠕虫感染后肺部或结肠炎诱导后肠道中抗炎和组织修复基因的诱导。相比之下，对于巨噬细胞中细胞因子依赖性诱导模式识别受体、细胞粘附或趋化性基因而言，凋亡细胞的识别并非必需。因此，凋亡细胞的检测可在空间上分隔或防止多效性可溶性细胞因子如IL-4或IL-13的过早或异位活性。
