Impaired Luminal Control of Intestinal Macrophage Maturation in Patients With Ulcerative Colitis During Remission
Journal article, 2021

Background & Aims: 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, therefore, was to determine the effects of fecal luminal factors derived from healthy donors and UC patients in remission on macrophage phenotype and function. Methods: 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 granulocyte-macrophage colony-stimulating factor without/with FS, stimulated with lipopolysaccharide, and macrophage phenotype and function were assessed. Fecal metabolomic profiles were analyzed by gas-chromatography/mass-spectrometry. Results: Fecal luminal factors derived from healthy donors were effective in down-regulating Toll-like receptor signaling, cytokine signaling, and antigen presentation in macrophages. Fecal luminal factors derived from UC patients in remission were less potent in inducing lipopolysaccharide hyporesponsiveness and modulating expression of genes involved in macrophage cytokine and Toll-like receptor signaling pathways. Although phagocytic and bactericidal abilities of macrophages were not affected by FS treatment, healthy FS-treated macrophages showed a greater ability to suppress cluster of differentiation 4+ T-cell activation and interferon γ secretion compared with UC remission FS-treated counterparts. Furthermore, metabolomic analysis showed differential fecal metabolite composition for healthy donors and UC patients in remission. Conclusions: Our data indicate that UC patients in remission lack luminal signals able to condition macrophages toward a hyporesponsive and tolerogenic phenotype, which may contribute to their persistent vulnerability to relapse.

Ulcerative Colitis




TLR Signaling


Lujain Maasfeh

University of Gothenburg

Anetta Härtlova

University of Gothenburg

Wallenberg Lab.

Stefan Isaksson

University of Gothenburg

Johanna Sundin

University of Gothenburg

Georgios Mavroudis

Kungälv Hospital

Otto Savolainen

Chalmers, Biology and Biological Engineering, Systems and Synthetic Biology

Hans Strid

Södra Älvsborg Hospital (SÄS)

Lena Öhman

University of Gothenburg

Maria K. Magnusson

University of Gothenburg

CMGH Cellular and Molecular Gastroenterology and Hepatology

2352-345X (eISSN)

Vol. 12 4 1415-1432

Subject Categories

Other Clinical Medicine

Gastroenterology and Hepatology






More information

Latest update