Macrophage dynamics are regulated by local macrophage proliferation and monocyte recruitment in injured pancreas
Van Gassen, Naomi × Van Overmeire, Eva Leuckx, Gunter Heremans, Yves De Groef, Sofie Elkrim, Yvon Gysemans, Conny Stijlemans, Benoît Van de Casteele, Mark De Baetselier, Patrick De Leu, Nico Heimberg, Harry Van Ginderachter, Jo A #
European Journal of Immunology vol:45 issue:5 pages:1482-93
Pancreas injury by partial duct ligation (PDL) activates a healing response, encompassing β-cell neogenesis and proliferation. Macrophages 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 macrophage types, designated MHC-II(lo) and MHC-II(hi) macrophages, the latter being predominant. MHC-II(lo) and MHC-II(hi) pancreas macrophages differed at the molecular level, with MHC-II(lo) macrophages 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) macrophage peak and ultimately a restoration of the MHC-II(hi) macrophage-dominated steady-state equilibrium. These intricate macrophage dynamics in PDL pancreas depended on monocyte recruitment by CCR2 and M-CSFR as well as on M-CSFR-dependent local macrophage proliferation. Functionally, MHC-II(lo) macrophages were more angiogenic. We further demonstrated that, at least in CCR2-KO mice, tissue macrophages, rather than Ly6C(hi) monocyte-derived macrophages, contributed to β-cell proliferation. Together, our study fully characterizes the macrophage subsets in the pancreas and clarifies the complex dynamics of macrophages after PDL injury. This article is protected by copyright. All rights reserved.