title: A dynamic spectrum of monocytes arising from the in situ reprogramming of CCR2+ monocytes at a site of sterile injury.
abstract: 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 (CCR2(hi)CX3CR1(low)) and nonclassical, patrolling, or alternative (CCR2(low)CX3CR1(hi)) 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 CCR2(hi)CX3CR1(low) 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 CCR2(hi)Cx3CR1(low) to CX3CR1(hi)CCR2(low) 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.
authors: Immunology Research Group, Snyder Institute for Chronic Diseases; Department of Microbiology, Immunology, and Infectious Diseases; and Department of Physiology and Pharmacology, University of Calgary, Calgary, Alberta T2N 4N1, Canada.
authors: Daniela
authors: D
authors: Dal-Secco
authors: Immunology Research Group, Snyder Institute for Chronic Diseases; Department of Microbiology, Immunology, and Infectious Diseases; and Department of Physiology and Pharmacology, University of Calgary, Calgary, Alberta T2N 4N1, Canada Immunology Research Group, Snyder Institute for Chronic Diseases; Department of Microbiology, Immunology, and Infectious Diseases; and Department of Physiology and Pharmacology, University of Calgary, Calgary, Alberta T2N 4N1, Canada.
authors: Jing
authors: J
authors: Wang
authors: Immunology Research Group, Snyder Institute for Chronic Diseases; Department of Microbiology, Immunology, and Infectious Diseases; and Department of Physiology and Pharmacology, University of Calgary, Calgary, Alberta T2N 4N1, Canada Immunology Research Group, Snyder Institute for Chronic Diseases; Department of Microbiology, Immunology, and Infectious Diseases; and Department of Physiology and Pharmacology, University of Calgary, Calgary, Alberta T2N 4N1, Canada.
authors: Zhutian
authors: Z
authors: Zeng
authors: Immunology Research Group, Snyder Institute for Chronic Diseases; Department of Microbiology, Immunology, and Infectious Diseases; and Department of Physiology and Pharmacology, University of Calgary, Calgary, Alberta T2N 4N1, Canada.
authors: Elzbieta
authors: E
authors: Kolaczkowska
authors: Immunology Research Group, Snyder Institute for Chronic Diseases; Department of Microbiology, Immunology, and Infectious Diseases; and Department of Physiology and Pharmacology, University of Calgary, Calgary, Alberta T2N 4N1, Canada.
authors: Connie H Y
authors: CH
authors: Wong
authors: Immunology Research Group, Snyder Institute for Chronic Diseases; Department of Microbiology, Immunology, and Infectious Diseases; and Department of Physiology and Pharmacology, University of Calgary, Calgary, Alberta T2N 4N1, Canada Immunology Research Group, Snyder Institute for Chronic Diseases; Department of Microbiology, Immunology, and Infectious Diseases; and Department of Physiology and Pharmacology, University of Calgary, Calgary, Alberta T2N 4N1, Canada.
authors: Björn
authors: B
authors: Petri
authors: Neuroinflammation Research Center, Department of Neurosciences, Lerner Research Institute, Cleveland Clinic, Cleveland, OH 44195.
authors: Richard M
authors: RM
authors: Ransohoff
authors: Gladstone Institute of Cardiovascular Disease and Cardiovascular Research Institute, Department of Medicine, University of California, San Francisco, San Francisco, CA 94143.
authors: Israel F
authors: IF
authors: Charo
authors: Immunology Research Group, Snyder Institute for Chronic Diseases; Department of Microbiology, Immunology, and Infectious Diseases; and Department of Physiology and Pharmacology, University of Calgary, Calgary, Alberta T2N 4N1, Canada Immunology Research Group, Snyder Institute for Chronic Diseases; Department of Microbiology, Immunology, and Infectious Diseases; and Department of Physiology and Pharmacology, University of Calgary, Calgary, Alberta T2N 4N1, Canada pkubes@ucalgary.ca cnjenne@ucalgary.ca.
authors: Craig N
authors: CN
authors: Jenne
authors: Immunology Research Group, Snyder Institute for Chronic Diseases; Department of Microbiology, Immunology, and Infectious Diseases; and Department of Physiology and Pharmacology, University of Calgary, Calgary, Alberta T2N 4N1, Canada Immunology Research Group, Snyder Institute for Chronic Diseases; Department of Microbiology, Immunology, and Infectious Diseases; and Department of Physiology and Pharmacology, University of Calgary, Calgary, Alberta T2N 4N1, Canada pkubes@ucalgary.ca cnjenne@ucalgary.ca.
authors: Paul
authors: P
authors: Kubes
mesh_terms: D000818:Animals; D000073883:CX3C Chemokine Receptor 1; D002465:Cell Movement / Q000276:immunology*; D065150:Cellular Reprogramming / Q000276:immunology*; D008099:Liver / Q000276:immunology / Q000293:injuries / Q000473:pathology; D051379:Mice; D018345:Mice, Knockout; D018613:Microscopy, Confocal; D009000:Monocytes / Q000276:immunology* / Q000473:pathology; D054390:Receptors, CCR2 / Q000276:immunology*; D019707:Receptors, Chemokine / Q000276:immunology; D014945:Wound Healing / Q000276:immunology*
chemical_list: D000073883:CX3C Chemokine Receptor 1; C515335:Ccr2 protein, mouse; C471885:Cx3cr1 protein, mouse; D054390:Receptors, CCR2; D019707:Receptors, Chemokine