The Presence of Interleukin-13 at Pancreatic ADM/PanIN Lesions Alters Macrophage Populations and Mediates Pancreatic Tumorigenesis

Cell Rep. 2017 May 16;19(7):1322-1333. doi: 10.1016/j.celrep.2017.04.052.


The contributions of the innate immune system to the development of pancreatic cancer are still ill defined. Inflammatory macrophages can initiate metaplasia of pancreatic acinar cells to a duct-like phenotype (acinar-to-ductal metaplasia [ADM]), which then gives rise to pancreatic intraepithelial neoplasia (PanIN) when oncogenic KRas is present. However, it remains unclear when and how this inflammatory macrophage population is replaced by tumor-promoting macrophages. Here, we demonstrate the presence of interleukin-13 (IL-13), which can convert inflammatory into Ym1+ alternatively activated macrophages, at ADM/PanIN lesions. We further show that Ym1+ macrophages release factors, such as IL-1ra and CCL2, to drive pancreatic fibrogenesis and tumorigenesis. Treatment of mice expressing oncogenic KRas under an acinar cell-specific promoter with a neutralizing antibody for IL-13 significantly decreased the accumulation of alternatively activated macrophages at these lesions, resulting in decreased fibrosis and lesion growth.

Keywords: CCL-2; IL-13; IL-1ra; PanIN; Tuft cells; interleukin-13; macrophages; metaplasia; pancreatic cancer; polarization.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Carcinogenesis / metabolism*
  • Carcinogenesis / pathology*
  • Carcinoma in Situ / metabolism*
  • Carcinoma in Situ / pathology*
  • Cell Line, Tumor
  • Cell Polarity
  • Cell Proliferation
  • Fibrosis
  • Inflammation / pathology
  • Interleukin-13 / metabolism*
  • Macrophages / pathology
  • Metaplasia
  • Mice
  • Neutralization Tests
  • Pancreatic Ducts / metabolism
  • Pancreatic Ducts / pathology*
  • Pancreatic Neoplasms / metabolism*
  • Pancreatic Neoplasms / pathology*


  • Interleukin-13