The Stimulation of Macrophages with TLR Ligands Supports Increased IL-19 Expression in Inflammatory Bowel Disease Patients and in Colitis Models

Anna Steinert; Ioannis Linas; Berna Kaya; Mohamed Ibrahim; Andreas Schlitzer; Petr Hruz; Katarina Radulovic; Luigi Terracciano; Andrew J Macpherson; Jan Hendrik Niess

doi:10.4049/jimmunol.1700350

The Stimulation of Macrophages with TLR Ligands Supports Increased IL-19 Expression in Inflammatory Bowel Disease Patients and in Colitis Models

J Immunol. 2017 Oct 1;199(7):2570-2584. doi: 10.4049/jimmunol.1700350. Epub 2017 Sep 1.

Authors

Anna Steinert^{1

2

3}, Ioannis Linas³, Berna Kaya^{1

2}, Mohamed Ibrahim^{4

5}, Andreas Schlitzer^{4

5

6}, Petr Hruz^{1

2}, Katarina Radulovic^{1

2}, Luigi Terracciano⁷, Andrew J Macpherson³, Jan Hendrik Niess^{8

2

3}

Affiliations

¹ Division of Gastroenterology and Hepatology, University Hospital Basel, 4031 Basel, Switzerland.
² Department of Biomedicine, University of Basel, 4031 Basel, Switzerland.
³ Division of Gastroenterology, Department of Clinical Research, University Clinic for Visceral Surgery and Medicine, University of Bern, 3010 Bern, Switzerland.
⁴ Department of Genomics and Immunoregulation, Life and Medical Science Institute, University of Bonn, 53115 Bonn, Germany.
⁵ Single Cell Genomics and Epigenomics Unit, German Center for Neurodegenerative Diseases, University of Bonn, 53115 Bonn, Germany.
⁶ Singapore Immunology Network, Agency for Science, Technology and Research, Singapore, 138648 Singapore; and.
⁷ Institute of Pathology, University Hospital Basel, University of Basel, 4031 Basel, Switzerland.
⁸ Division of Gastroenterology and Hepatology, University Hospital Basel, 4031 Basel, Switzerland; janhendrik.niess@usb.ch.

PMID: 28864472
DOI: 10.4049/jimmunol.1700350

Abstract

IL-19, a member of the IL-10 cytokine family that signals through the IL-20 receptor type I (IL-20Rα:IL-20Rβ), is a cytokine whose function is not completely known. In this article, we show that the expression of IL19 in biopsies of patients with active ulcerative colitis was increased compared with patients with quiescent ulcerative colitis and that colitis was attenuated in IL-19-deficient mice. The disruption of the epithelial barrier with dextran sodium sulfate leads to increased IL-19 expression. Attenuated colitis in IL-19-deficient animals was associated with reduced numbers of IL-6-producing macrophages in the inflamed colonic lamina propria. Microbial-driven expression of IL-19 by intestinal macrophages may contribute to the pathogenesis of inflammatory bowel disease.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Biopsy
Colitis / immunology
Colitis, Ulcerative / immunology*
Colitis, Ulcerative / pathology
Dextran Sulfate / administration & dosage
Disease Models, Animal
Humans
Inflammatory Bowel Diseases / immunology*
Inflammatory Bowel Diseases / pathology
Interleukin-10 / deficiency
Interleukin-10 / genetics*
Interleukin-10 / immunology
Interleukin-10 / metabolism
Interleukin-6 / biosynthesis
Interleukin-6 / immunology
Interleukins / genetics*
Interleukins / immunology
Interleukins / metabolism
Intestines / cytology
Intestines / immunology
Intestines / pathology
Ligands
Macrophages
Mice
Mucous Membrane / immunology
Signal Transduction
Toll-Like Receptors / immunology*
Toll-Like Receptors / metabolism

Substances

IL19 protein, human
Il19 protein, mouse
Interleukin-6
Interleukins
Ligands
Toll-Like Receptors
Interleukin-10
Dextran Sulfate