期刊
JCI INSIGHT
卷 2, 期 15, 页码 -出版社
AMER SOC CLINICAL INVESTIGATION INC
DOI: 10.1172/jci.insight.93834
关键词
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资金
- Life Sciences Discovery Fund program project grant
- Diabetes Research Connection
- NIH [R01 AI093808]
- NIH/National Cancer Institute Cancer Center Support Grant [P30 CA008748]
- Medical University of South Carolina start-up funds
- Genomics Shared Resource, Hollings Cancer Center, Medical University of South Carolina
- Hollings Cancer Center, Medical University of South Carolina Support Grant [P30 CA 138313]
Organ-specific patterns of myeloid cells may contribute tissue-specific growth and/ or regenerative potentials. The perinatal stage of pancreas development marks a time characterized by maximal proliferation of pancreatic islets, ensuring the maintenance of glucose homeostasis throughout life. Ontogenically distinct CX3CR1(+) and CCR2(+) macrophage populations have been reported in the adult pancreas, but their functional contribution to islet cell growth at birth remains unknown. Here, we uncovered a temporally restricted requirement for CCR2(+) myeloid cells in the perinatal proliferation of the endocrine pancreatic epithelium. CCR2(+) macrophages are transiently enriched over CX3CR1(+) subsets in the neonatal pancreas through both local expansion and recruitment of immature precursors. Using CCR2-specific depletion models, we show that loss of this myeloid population leads to a striking reduction in beta cell proliferation, dysfunctional islet phenotypes, and glucose intolerance in newborns. Replenishment of pancreatic CCR2(+) myeloid compartments by adoptive transfer rescues these defects. Gene profiling identifies pancreatic CCR2(+) myeloid cells as a prominent source of IGF2, which contributes to IGF1R-mediated islet proliferation. These findings uncover proproliferative functions of CCR2(+) myeloid subsets and identify myeloid-dependent regulation of IGF signaling as a local cue supporting pancreatic proliferation.
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