Affordable Access

deepdyve-link
Publisher Website

Impaired luminal control of intestinal macrophage maturation in patients with ulcerative colitis during remission.

Authors
  • Maasfeh, Lujain1
  • Hartlova, Anetta2
  • Isaksson, Stefan1
  • Sundin, Johanna3
  • Mavroudis, Georgios4
  • Savolainen, Otto5
  • Strid, Hans6
  • Öhman, Lena1
  • Magnusson, Maria K7
  • 1 Department of Microbiology and Immunology, Institute of Biomedicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden. , (Sweden)
  • 2 Department of Microbiology and Immunology, Institute of Biomedicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden,; Wallenberg Centre for molecular and translational medicine, University of Gothenburg, Sweden. , (Sweden)
  • 3 Department of Microbiology and Immunology, Institute of Biomedicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden,; Department of Internal Medicine and Clinical Nutrition, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden. , (Sweden)
  • 4 Department of Internal Medicine, Kungälv Hospital, Kungälv, Sweden. , (Sweden)
  • 5 Department of Biology and Biological Engineering, Chalmers University of Technology, Gothenburg, Sweden. , (Sweden)
  • 6 Department of Internal Medicine, Södra Älvsborg Hospital, Borås, Sweden. , (Sweden)
  • 7 Department of Microbiology and Immunology, Institute of Biomedicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden,. Electronic address: [email protected] , (Sweden)
Type
Published Article
Journal
Cellular and Molecular Gastroenterology and Hepatology
Publisher
Elsevier
Publication Date
Jun 11, 2021
Identifiers
DOI: 10.1016/j.jcmgh.2021.06.004
PMID: 34126236
Source
Medline
Keywords
Language
English
License
Unknown

Abstract

Intestinal macrophages adopt a hyporesponsive phenotype through education by local signals. Lack of proper macrophage maturation in patients with ulcerative colitis (UC) in remission may initiate gut inflammation. The aim was therefore to determine the effects of fecal luminal factors derived from healthy donors and UC patients in remission on macrophage phenotype and function. Fecal supernatants (FS) were extracted from fecal samples of healthy subjects and UC patients in remission. Monocytes were matured into macrophages in the presence of GM-CSF without/with FS, stimulated with lipopolysaccharide (LPS) and macrophage phenotype and function were assessed. Fecal metabolomic profiles were analyzed by gas-chromatography/mass-spectrometry. Fecal luminal factors derived from healthy donors were effective in downregulating TLR signaling, cytokine signaling and antigen presentation in macrophages. Fecal luminal factors derived from UC patients in remission were less potent in inducing LPS hyporesponsiveness and modulating expression of genes involved in macrophage cytokine and TLR signaling pathways. While phagocytic and bactericidal abilities of macrophages were not affected by FS treatment, healthy FS treated macrophages showed a greater ability to suppress CD4+ T cell activation and IFNγ secretion compared to UC remission FS treated counterparts. Furthermore, metabolomic analysis revealed differential fecal metabolite composition for healthy donors and UC patients in remission. Our data indicate that UC patients in remission lack luminal signals able to condition macrophages towards a hyporesponsive and tolerogenic phenotype which may contribute to their persistent vulnerability to relapse. Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.

Report this publication

Statistics

Seen <100 times