title: Macrophage dynamics are regulated by local macrophage proliferation and monocyte recruitment in injured pancreas.
abstract: Pancreas injury by partial duct ligation (PDL) activates a healing response, encompassing β-cell neogenesis and proliferation. Macrophages (MΦs) were recently shown to promote β-cell proliferation after PDL, but they remain poorly characterized. We assessed myeloid cell diversity and the factors driving myeloid cell dynamics following acute pancreas injury by PDL. In naive and sham-operated pancreas, the myeloid cell compartment consisted mainly of two distinct tissue-resident MΦ types, designated MHC-II(lo) and MHC-II(hi) MΦs, the latter being predominant. MHC-II(lo) and MHC-II(hi) pancreas MΦs differed at the molecular level, with MHC-II(lo) MΦs being more M2-activated. After PDL, there was an early surge of Ly6C(hi) monocyte infiltration in the pancreas, followed by a transient MHC-II(lo) MΦ peak and ultimately a restoration of the MHC-II(hi) MΦ-dominated steady-state equilibrium. These intricate MΦ dynamics in PDL pancreas depended on monocyte recruitment by C-C chemokine receptor 2 and macrophage-colony stimulating factor receptor as well as on macrophage-colony stimulating factor receptor-dependent local MΦ proliferation. Functionally, MHC-II(lo) MΦs were more angiogenic. We further demonstrated that, at least in C-C chemokine receptor 2-KO mice, tissue MΦs, rather than Ly6C(hi) monocyte-derived MΦs, contributed to β-cell proliferation. Together, our study fully characterizes the MΦ subsets in the pancreas and clarifies the complex dynamics of MΦs after PDL injury.
authors: Diabetes Research Center, Vrije Universiteit Brussel, Brussels, Belgium.
authors: Naomi
authors: N
authors: Van Gassen
authors: Myeloid Cell Immunology Laboratory, VIB, Brussels, Belgium.|Laboratory of Cellular and Molecular Immunology, Vrije Universiteit Brussel, Brussels, Belgium.
authors: Eva
authors: E
authors: Van Overmeire
authors: Diabetes Research Center, Vrije Universiteit Brussel, Brussels, Belgium.
authors: Gunter
authors: G
authors: Leuckx
authors: Diabetes Research Center, Vrije Universiteit Brussel, Brussels, Belgium.
authors: Yves
authors: Y
authors: Heremans
authors: Diabetes Research Center, Vrije Universiteit Brussel, Brussels, Belgium.
authors: Sofie
authors: S
authors: De Groef
authors: Diabetes Research Center, Vrije Universiteit Brussel, Brussels, Belgium.
authors: Ying
authors: Y
authors: Cai
authors: Myeloid Cell Immunology Laboratory, VIB, Brussels, Belgium.|Laboratory of Cellular and Molecular Immunology, Vrije Universiteit Brussel, Brussels, Belgium.
authors: Yvon
authors: Y
authors: Elkrim
authors: Laboratory of Clinical and Experimental Endocrinology, Department of Clinical and Experimental Medicine, KU Leuven, Leuven, Belgium.
authors: Conny
authors: C
authors: Gysemans
authors: Myeloid Cell Immunology Laboratory, VIB, Brussels, Belgium.|Laboratory of Cellular and Molecular Immunology, Vrije Universiteit Brussel, Brussels, Belgium.
authors: Benoît
authors: B
authors: Stijlemans
authors: Diabetes Research Center, Vrije Universiteit Brussel, Brussels, Belgium.
authors: Mark
authors: M
authors: Van de Casteele
authors: Myeloid Cell Immunology Laboratory, VIB, Brussels, Belgium.|Laboratory of Cellular and Molecular Immunology, Vrije Universiteit Brussel, Brussels, Belgium.
authors: Patrick
authors: P
authors: De Baetselier
authors: Diabetes Research Center, Vrije Universiteit Brussel, Brussels, Belgium.
authors: Nico
authors: N
authors: De Leu
authors: Diabetes Research Center, Vrije Universiteit Brussel, Brussels, Belgium.
authors: Harry
authors: H
authors: Heimberg
authors: Myeloid Cell Immunology Laboratory, VIB, Brussels, Belgium.|Laboratory of Cellular and Molecular Immunology, Vrije Universiteit Brussel, Brussels, Belgium.
authors: Jo A
authors: JA
authors: Van Ginderachter
mesh_terms: D000818:Animals; D000950:Antigens, Ly / Q000378:metabolism; D002465:Cell Movement / Q000276:immunology; D049109:Cell Proliferation; D060833:Cellular Microenvironment / Q000276:immunology; D000949:Histocompatibility Antigens Class II / Q000378:metabolism; D008026:Ligation; D008262:Macrophage Activation; D008264:Macrophages / Q000276:immunology* / Q000473:pathology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D009000:Monocytes / Q000276:immunology* / Q000473:pathology*; D022423:Myeloid Cells / Q000145:classification / Q000276:immunology / Q000473:pathology; D010179:Pancreas / Q000276:immunology* / Q000293:injuries* / Q000473:pathology; D010183:Pancreatic Ducts / Q000293:injuries; D016186:Receptor, Macrophage Colony-Stimulating Factor / Q000378:metabolism; D012038:Regeneration / Q000276:immunology
chemical_list: D000950:Antigens, Ly; D000949:Histocompatibility Antigens Class II; C494192:Ly-6C antigen, mouse; D016186:Receptor, Macrophage Colony-Stimulating Factor
keywords: MΦ activation; MΦ heterogeneity; MΦ proliferation; Pancreas inflammation