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

Geou Yarh Liou, Ligia Bastea, Alicia Fleming, Heike Döppler, Brandy H. Edenfield, David W. Dawson, Lizhi Zhang, Nabeel Bardeesy, Peter Storz

Research output: Contribution to journalArticle

22 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1322-1333
Number of pages12
JournalCell Reports
Volume19
Issue number7
DOIs
StatePublished - May 16 2017

Fingerprint

Interleukin-13
Macrophages
Metaplasia
Carcinogenesis
Population
Neoplasms
Acinar Cells
Interleukin 1 Receptor Antagonist Protein
Immune system
Neutralizing Antibodies
Pancreatic Neoplasms
Ducts
Tumors
Immune System
Fibrosis
Phenotype
Growth

Keywords

  • CCL-2
  • IL-13
  • IL-1ra
  • interleukin-13
  • macrophages
  • metaplasia
  • pancreatic cancer
  • PanIN
  • polarization
  • Tuft cells

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

The Presence of Interleukin-13 at Pancreatic ADM/PanIN Lesions Alters Macrophage Populations and Mediates Pancreatic Tumorigenesis. / Liou, Geou Yarh; Bastea, Ligia; Fleming, Alicia; Döppler, Heike; Edenfield, Brandy H.; Dawson, David W.; Zhang, Lizhi; Bardeesy, Nabeel; Storz, Peter.

In: Cell Reports, Vol. 19, No. 7, 16.05.2017, p. 1322-1333.

Research output: Contribution to journalArticle

Liou, Geou Yarh ; Bastea, Ligia ; Fleming, Alicia ; Döppler, Heike ; Edenfield, Brandy H. ; Dawson, David W. ; Zhang, Lizhi ; Bardeesy, Nabeel ; Storz, Peter. / The Presence of Interleukin-13 at Pancreatic ADM/PanIN Lesions Alters Macrophage Populations and Mediates Pancreatic Tumorigenesis. In: Cell Reports. 2017 ; Vol. 19, No. 7. pp. 1322-1333.
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