Dataset Information

IL-12 and Mucosal CD14+ Monocyte-Like Cells Induce IL-8 in Colonic Memory CD4+ T Cells of Patients With Ulcerative Colitis but not Crohn's Disease.

ABSTRACT:

Background and aims

CD14+ mononuclear phagocytes [MNPs] and T cells infiltrate colon in ulcerative colitis [UC]. Here we investigated how CD14+ MNPs and the cytokines they produce shape the colonic effector T cell profile.

Methods

Colonic or mesenteric lymph node [mLNs] CD4+ T cells isolated from UC or Crohn's disease [CD] patients were stimulated with cytokines or autologous CD14+ MNPs. Cytokine expression was assessed by intracytoplasmic staining and multiplex ELISA. Unsupervised phenotypic multicolour analysis of colonic CD14+ MNPs was performed using the FlowSOM algorithm.

Results

Among CD14+CD64+HLA-DR+SIRP??+ MNPs, only the pro-inflammatory cytokine-producing CD163- subpopulation accumulated in inflamed UC colon and promoted mucosal IL-1?-dependent Th17, Th17/Th1, Th17/Th22 but not Th1 responses. Unsupervised phenotypic analysis of CD14+CD64+ MNPs segregated CD163- monocyte-like cells and CD163+ macrophages. Unexpectedly, IL-12, IL-1? and CD163-, but not CD163+, cells induced IL-8 expression in colonic CD4+ T cells, which co-expressed IFN-? and/or IL-17 in UC and not CD. The CD163- monocyte-like cells increased the frequency of IL-8+IL-17+/-IFN-??+/- T cells through IL-1? and IL-12. Finally, colonic IL-8+ T cells co-expressing GM-CSF, TNF-? and IL-6 were detected ex vivo and, promoted by IL-12 in the mucosa and mLNs in UC only.

Conclusions

Our findings established a link between monocyte-like CD163- MNPs, IL-12, IL-1? and the detection of colonic memory IL-8-producing CD4+ T cells, which might all contribute to the pathogenesis of UC.

SUBMITTER: Chapuy L

PROVIDER: S-EPMC6930004 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature

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Publications

IL-12 and Mucosal CD14+ Monocyte-Like Cells Induce IL-8 in Colonic Memory CD4+ T Cells of Patients With Ulcerative Colitis but not Crohn's Disease.

Chapuy Laurence L Bsat Marwa M Rubio Manuel M Sarkizova Sisi S Therrien Amélie A Bouin Mickael M Orlicka Katarzina K Weber Audrey A Soucy Geneviève G Villani Alexandra-Chloé AC Sarfati Marika M

Journal of Crohn's & colitis 20200101 1

<h4>Background and aims</h4>CD14+ mononuclear phagocytes [MNPs] and T cells infiltrate colon in ulcerative colitis [UC]. Here we investigated how CD14+ MNPs and the cytokines they produce shape the colonic effector T cell profile.<h4>Methods</h4>Colonic or mesenteric lymph node [mLNs] CD4+ T cells isolated from UC or Crohn's disease [CD] patients were stimulated with cytokines or autologous CD14+ MNPs. Cytokine expression was assessed by intracytoplasmic staining and multiplex ELISA. Unsupervise ...[more]

PMID: 31206576

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Project description:BackgroundWe aimed to identify the risk factors associated with colonic cytomegalovirus (CMV) infection in ulcerative colitis (UC) and to compare the clinical course between antiviral therapy-treated and -untreated groups in mucosal CMV-polymerase chain reaction (PCR) -positive cases.MethodsWe retrospectively selected 46 UC patients (>15 years old) in active phase who underwent colonoscopy with biopsy and were analyzed for CMV infection by mucosal PCR between October 2011 and December 2015 at our institution. Colonic CMV in inflamed mucosa was detected using quantitative real-time PCR. The clinical course was evaluated, including need for drug therapy/surgery or drug therapy intensification. In addition, we evaluated the clinical course between CMV-DNA- cases and CMV-DNA+ cases with low viral load.ResultsAt baseline, CMV-DNA+ patients were significantly older, had higher endoscopic scores, and required higher corticosteroid doses during the past 4 weeks than CMV-DNA- patients (p< 0.05). No significant differences were observed in disease duration, disease distribution, laboratory data, or use of other medication between CMV-DNA+ and CMV-DNA- patients. In the anti-CMV-treated group with a median (range) DNA load of 16,000 (9,000-36,400), 3patients achieved remission without additional UC therapy, 2 required additional UC therapy, and 1 required colectomy despite azathioprine and infliximab therapy. In the CMV-untreated group with a median (range) DNA load of 919 (157-5,480), all patients achieved remission with UC therapy alone. No significant difference was observed in the clinical course between CMV-DNA- cases and CMV-DNA+ cases with low viral loads.ConclusionsAging, endoscopic UC activity, and corticosteroid dose predispose to colonic CMV infection, as determined by mucosal PCR, in UC. UC treatment without anti-CMV therapy may be warranted, particularly in patients with low-load CMV-DNA. Anti-CMV therapy alone does not always achieve clinical response in UC even in cases with high-load PCR.

Dataset Information

IL-12 and Mucosal CD14+ Monocyte-Like Cells Induce IL-8 in Colonic Memory CD4+ T Cells of Patients With Ulcerative Colitis but not Crohn's Disease.

Background and aims

Methods

Results

Conclusions

Publications

IL-12 and Mucosal CD14+ Monocyte-Like Cells Induce IL-8 in Colonic Memory CD4+ T Cells of Patients With Ulcerative Colitis but not Crohn's Disease.

Similar Datasets

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