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

Cell Reports
Geou-Yarh LiouPeter Storz

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.

Citations

Feb 11, 2018·The Journal of Physiology·Anne R Meyer, James R Goldenring
Jan 31, 2018·Journal of Immunology Research·Geou-Yarh Liou
Nov 13, 2018·Annual Review of Physiology·Yaqing ZhangMarina Pasca di Magliano
Sep 2, 2017·Nature Reviews. Cancer·Veronique Giroux, Anil K Rustgi
Jun 1, 2019·Expert Review of Anticancer Therapy·Veethika Pandey, Peter Storz
Sep 19, 2019·Annual Review of Pathology·Massimo LocatiAlberto Mantovani
Aug 3, 2020·Molecular Oncology·James O JonesJacqueline D Shields
Sep 5, 2020·Immunity, Inflammation and Disease·Andrea F CruzFarzad Esni
Sep 10, 2020·Journal of Hepato-biliary-pancreatic Sciences·Ariel A ArtetaNora Cardona-Castro
Jan 16, 2019·BioMed Research International·Mingli NiMingzhi Zhang
Oct 19, 2019·Journal of Cellular Physiology·Jie WanHuaxi Xu
Sep 1, 2017·The FEBS Journal·Peter J Murray
Dec 21, 2018·World Journal of Clinical Cases·Takahiro SeimiyaKazuhiko Koike
Aug 15, 2020·Frontiers in Oncology·Ariel A ArtetaNora Cardona-Castro
Jun 6, 2018·International Journal of Molecular Sciences·Claudia GeismannAlexander Arlt
May 14, 2020·Nature Reviews. Clinical Oncology·Won Jin HoLei Zheng
May 15, 2018·International Journal of Cancer. Journal International Du Cancer·Faraz BishehsariAli Keshavarzian
Oct 21, 2020·Nature Medicine·Daniela Cerezo-WallisMaría S Soengas
Nov 13, 2020·Expert Opinion on Therapeutic Targets·Yuning YangNathaniel Weygant
Dec 17, 2020·Biomedicines·Yu-Ching FanYuan-Chin Tsai
Oct 24, 2020·Trends in Pharmacological Sciences·Andrei-Florian StoicaSiim Pauklin
Apr 24, 2020·Endocrine, Metabolic & Immune Disorders Drug Targets·Hemanth K KandikattuAnil Mishra
Mar 31, 2021·Cancer Metastasis Reviews·Victor Delprat, Carine Michiels
Apr 4, 2021·International Journal of Molecular Sciences·Jingwei ShiMarko Kornmann
Jan 21, 2019·Gastroenterology·Vinod P BalachandranStephanie K Dougan
Apr 7, 2021·Pharmacological Research : the Official Journal of the Italian Pharmacological Society·Xufeng TaoGary Guishan Xiao
Mar 23, 2020·Gastroenterology·Peter Storz, Howard C Crawford
Aug 17, 2021·Frontiers in Cell and Developmental Biology·Yiyi LiangHong Tu
Jun 4, 2019·Pharmacology & Therapeutics·Meredith L Stone, Gregory L Beatty
Dec 15, 2021·Journal of Zhejiang University. Science. B·Jicheng ZhangNing Pu

❮ Previous
Next ❯

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.