CD1a-Expressing Monocytes As Mediators of Inflammation in Ulcerative Colitis

Overview

Journal Inflamm Bowel Dis

Publisher Oxford University Press

Specialty Gastroenterology

Date 2018 May 23

PMID 29788291

Citations 14

Authors

Omar Al-Amodi

Henrika Jodeleit

Florian Beigel

Eckhard Wolf

Matthias Siebeck

Roswitha Gropp

Affiliations

Soon will be listed here.

Abstract

Background: CD1a-expressing CD14+ monocytes have been identified as inducers of autoreactive T cells. In this study, the link between inflammatory and metabolic signals and CD1a-expressing monocytes in vitro and in vivo was examined, and CD1a was evaluated as a potential therapeutic target for treatment of ulcerative colitis (UC).

Methods: Peripheral blood mononuclear cells (PBMCs) from UC patients and non-UC donors were incubated with phosphatidylcholine (PC) for 2 and 7 days and subjected to flow cytometric analysis. Triacylglycerol (TAG) and cholesterol levels and frequencies of CD14+ CD1a+ monocytes were determined in a mouse model of UC that is based on NOD/scid IL2Rγnull mice reconstituted with PBMCs from UC patients (NSG-UC). NSG-UC mice were treated with anti-CD1a antibodies. Response to treatment was determined by clinical and histological scores, flow cytometric analysis of human leucocytes from the spleen and colon, and expression levels of TGFß1, HGF, IFNγ, and TARC.

Results: Incubation of PBMCs with PC resulted in an increase of the frequency of CD1a+ CD14+ monocytes at the expense of CCR2-, CD86-, and TSLPR-expressing CD14+ monocytes. CD1a+ CD14+ monocytes induced the activation of CD4+ T cells and differentiation of Th cells. In vivo, TAG and cholesterol levels increased upon inflammation and correlated positively with CD14+ CD1a+ monocytes. NSG-UC mice benefitted from treatment with anti-CD1a antibodies, as indicated by a reduced histological score and reduced frequencies of CD1a+ CD14+ monocytes in the colon and spleen of mice.

Conclusion: CD1a-expressing monocytes might act as sensors and mediators of inflammation in UC. Mice benefitted from treatment with anti-CD1a antibodies.

Citing Articles

Origin and Function of Monocytes in Inflammatory Bowel Disease.

Liao X, Liu J, Guo X, Meng R, Zhang W, Zhou J J Inflamm Res. 2024; 17:2897-2914.

PMID: 38764499 PMC: 11100499. DOI: 10.2147/JIR.S450801.

NOD/Scid IL2Rγ Mice Reconstituted with PBMCs from Patients with Atopic Dermatitis or Psoriasis Vulgaris Reflect the Respective Phenotype.

Schindler M, Schuster-Winkelmann P, Wess V, Czell S, Rueff F, Wollenberg A JID Innov. 2024; 4(3):100268.

PMID: 38736522 PMC: 11087984. DOI: 10.1016/j.xjidi.2024.100268.

Humanized NSG Mouse Models as a Preclinical Tool for Translational Research in Inflammatory Bowel Diseases.

Wess V, Schuster-Winkelmann P, Karatekin Y, Malik S, Beigel F, Kuhn F Int J Mol Sci. 2023; 24(15).

PMID: 37569722 PMC: 10418464. DOI: 10.3390/ijms241512348.

CD1a promotes systemic manifestations of skin inflammation.

Hardman C, Chen Y, Wegrecki M, Ng S, Murren R, Mangat D Nat Commun. 2022; 13(1):7535.

PMID: 36477177 PMC: 9729296. DOI: 10.1038/s41467-022-35071-1.

Role of Group 1 CD1-Restricted T Cells in Host Defense and Inflammatory Diseases.

Morgun E, Cao L, Wang C Crit Rev Immunol. 2022; 41(4):1-21.

PMID: 35381140 PMC: 10128144. DOI: 10.1615/CritRevImmunol.2021040089.

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