title: Structural environment built by AKAP12+ colon mesenchymal cells drives M2 macrophages during inflammation recovery.
abstract: Macrophages exhibit phenotypic plasticity, as they have the ability to switch their functional phenotypes during inflammation and recovery. Simultaneously, the mechanical environment actively changes. However, how these dynamic alterations affect the macrophage phenotype is unknown. Here, we observed that the extracellular matrix (ECM) constructed by AKAP12+ colon mesenchymal cells (CMCs) generated M2 macrophages by regulating their shape during recovery. Notably, rounded macrophages were present in the linear and loose ECM of inflamed colons and polarized to the M1 phenotype. In contrast, ramified macrophages emerged in the contracted ECM of recovering colons and mainly expressed M2 macrophage markers. These contracted structures were not observed in the inflamed colons of AKAP12 knockout (KO) mice. Consequently, the proportion of M2 macrophages in inflamed colons was lower in AKAP12 KO mice than in WT mice. In addition, clinical symptoms and histological damage were more severe in AKAP12 KO mice than in WT mice. In experimentally remodeled collagen gels, WT CMCs drove the formation of a more compacted structure than AKAP12 KO CMCs, which promoted the polarization of macrophages toward an M2 phenotype. These results demonstrated that tissue contraction during recovery provides macrophages with the physical cues that drive M2 polarization.
authors.affiliation: SNU-Harvard NeuroVascular Protection Research Center, College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul, 151-742, Korea.
authors.forename: Jun-Mo
authors.initials: JM
authors.lastname: Yang
authors.affiliation: SNU-Harvard NeuroVascular Protection Research Center, College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul, 151-742, Korea.
authors.forename: Hye Shin
authors.initials: HS
authors.lastname: Lee
authors.affiliation: SNU-Harvard NeuroVascular Protection Research Center, College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul, 151-742, Korea.
authors.forename: Ji Hae
authors.initials: JH
authors.lastname: Seo
authors.affiliation: SNU-Harvard NeuroVascular Protection Research Center, College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul, 151-742, Korea.
authors.forename: Ji-Hyeon
authors.initials: JH
authors.lastname: Park
authors.affiliation: Department of Cancer Genetics, Roswell Park Cancer Institute, Buffalo, NY 14263, USA.
authors.forename: Irwin H
authors.initials: IH
authors.lastname: Gelman
authors.affiliation: Neuroprotection Research Laboratory, Departments of Radiology and Neurology, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA 02129, USA.
authors.forename: Eng H
authors.initials: EH
authors.lastname: Lo
authors.affiliation: SNU-Harvard NeuroVascular Protection Research Center, College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul, 151-742, Korea.|Crop Biotechnology Institute, GreenBio Science and Technology, Seoul National University, Pyeongchang 25354, Republic of Korea.
authors.forename: Kyu-Won
authors.initials: KW
authors.lastname: Kim
mesh_terms: D054758:A Kinase Anchor Proteins / Q000235:genetics / Q000378:metabolism; D000818:Animals; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism; D002454:Cell Differentiation; D002478:Cells, Cultured; D003106:Colon / Q000166:cytology; D005109:Extracellular Matrix / Q000378:metabolism*; D007249:Inflammation / Q000378:metabolism; D008264:Macrophages / Q000166:cytology* / Q000378:metabolism; D059630:Mesenchymal Stem Cells / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL
chemical_list: D054758:A Kinase Anchor Proteins; C491161:Akap12 protein, mouse; D018797:Cell Cycle Proteins