Macrophage dynamics are regulated by local macrophage proliferation and monocyte recruitment in injured pancreas.

Pancreas injury by partial duct ligation (PDL) activates a healing response, encompassing -cell neogenesis and proliferation. Macrophages (M phi s) were recently shown to promote -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 M phi types, designated MHC-IIlo and MHC-IIhi M phi s, the latter being predominant. MHC-IIlo and MHC-IIhi pancreas M phi s differed at the molecular level, with MHC-IIlo M phi s being more M2-activated. After PDL, there was an early surge of Ly6C(hi) monocyte infiltration in the pancreas, followed by a transient MHC-IIlo M phi peak and ultimately a restoration of the MHC-IIhi M phi-dominated steady-state equilibrium. These intricate M phi 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 M phi proliferation. Functionally, MHC-IIlo M phi s were more angiogenic. We further demonstrated that, at least in C-C chemokine receptor 2-KO mice, tissue M phi s, rather than Ly6C(hi) monocyte-derived M phi s, contributed to -cell proliferation. Together, our study fully characterizes the M phi subsets in the pancreas and clarifies the complex dynamics of M phi s after PDL injury.