A dynamic spectrum of monocytes arising from the in situ reprogramming of CCR2+ monocytes at a site of sterile injury

Journal of Experimental Medicine - Tập 212 Số 4 - Trang 447-456 - 2015
Daniela Dal-Secco1,2,3, Jing Wang1,2,3, Zhutian Zeng1,2,3, Elżbieta Kołaczkowska1,2,3, Connie H. Y. Wong1,2,3, Björn Petri1,2,3, Richard M. Ransohoff4, Israel Charo5, Craig N. Jenne1,2,3, Paul Kubes1,2,3
1Department of Microbiology, Immunology, and Infectious Diseases 1 ; 2 ; and 3
2Department of Physiology and Pharmacology, University of Calgary, Calgary, Alberta T2N 4N1, Canada 1 ; 2 ; and 3
3Immunology Research Group, Snyder Institute for Chronic Diseases 1 ; 2 ; and 3
4Neuroinflammation Research Center, Department of Neurosciences, Lerner Research Institute, Cleveland Clinic, Cleveland, OH 44195 4
5Gladstone Institute of Cardiovascular Disease and Cardiovascular Research Institute, Department of Medicine, University of California, San Francisco, San Francisco, CA 94143 5

Tóm tắt

Monocytes are recruited from the blood to sites of inflammation, where they contribute to wound healing and tissue repair. There are at least two subsets of monocytes: classical or proinflammatory (CCR2hiCX3CR1low) and nonclassical, patrolling, or alternative (CCR2lowCX3CR1hi) monocytes. Using spinning-disk confocal intravital microscopy and mice with fluorescent reporters for each of these subsets, we were able to track the dynamic spectrum of monocytes that enter a site of sterile hepatic injury in vivo. We observed that the CCR2hiCX3CR1low monocytes were recruited early and persisted for at least 48 h, forming a ringlike structure around the injured area. These monocytes transitioned, in situ, from CCR2hiCx3CR1low to CX3CR1hiCCR2low within the ringlike structure and then entered the injury site. This phenotypic conversion was essential for optimal repair. These results demonstrate a local, cytokine driven reprogramming of classic, proinflammatory monocytes into nonclassical or alternative monocytes to facilitate proper wound-healing.

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Journal of Experimental Medicine

Tập 212 Số 4

447-456

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