scholarly journals Circulating CD4+and CD8+T cells are activated in inflammatory bowel disease and are associated with plasma markers of inflammation

Immunology ◽  
2013 ◽  
Vol 140 (1) ◽  
pp. 87-97 ◽  
Author(s):  
Nicholas T. Funderburg ◽  
Samantha R. Stubblefield Park ◽  
Hannah C. Sung ◽  
Gareth Hardy ◽  
Brian Clagett ◽  
...  
Keyword(s):  
Inflammatory Bowel Disease ◽  
T Cells ◽  
Cd8 T Cells ◽  
Bowel Disease ◽  
Markers Of Inflammation ◽  
Inflammatory Bowel ◽  
Plasma Markers

scholarly journals New Insights on CD8+ T Cells in Inflammatory Bowel Disease and Therapeutic Approaches

2021 ◽  
Vol 12 ◽  
Author(s):  
Rosaely Casalegno Garduño ◽  
Jan Däbritz
Keyword(s):  
Inflammatory Bowel Disease ◽  
T Cells ◽  
Cd8 T Cells ◽  
Bowel Disease ◽  
Positive Outcome ◽  
T Cell Subsets ◽  
Therapeutic Approaches ◽  
Therapeutic Value ◽  
Inflammatory Bowel

CD8+ T cells are involved in the pathogenesis of inflammatory bowel disease (IBD), a complex multifactorial chronic disease. Here, we present an overview of the current research with the controversial findings of CD8+ T cell subsets and discuss some possible perspectives on their therapeutic value in IBD. Studies on the role of CD8+ T cells in IBD have contradictory outcomes, which might be related to the heterogeneity of the cells. Recent data suggest that cytotoxic CD8+ T cells (Tc1) and interleukin (IL) 17-producing CD8+ (Tc17) cells contribute to the pathogenesis of IBD. Moreover, subsets of regulatory CD8+ T cells are abundant at sites of inflammation and can exhibit pro-inflammatory features. Some subsets of tissue resident memory CD8+ T cells (Trm) might be immunosuppressant, whereas others might be pro-inflammatory. Lastly, exhausted T cells might indicate a positive outcome for patients. The function and plasticity of different subsets of CD8+ T cells in health and IBD remain to be further investigated in a challenging field due to the limited availability of mucosal samples and adequate controls.

scholarly journals P111 Elucidation of inflammatory infiltration of myenteric plexus in IBD

2020 ◽  
Vol 14 (Supplement_1) ◽  
pp. S191-S191
Author(s):  
J J Wiese ◽  
A Fascì ◽  
A A Kühl ◽  
B Siegmund ◽  
M S Prüß ◽  
...  
Keyword(s):  
Inflammatory Bowel Disease ◽  
T Cells ◽  
B Cells ◽  
Cd8 T Cells ◽  
Immune Cells ◽  
Bowel Disease ◽  
Myenteric Plexus ◽  
Pain Catastrophizing ◽  
Visual Analogue Scale Pain ◽  
Inflammatory Bowel

Abstract Background Since IBD is frequently associated with chronic abdominal pain and visceral hypersensitivity, affections to the sensory nerves within the ENS appear to be pivotal. In both inflammatory bowel diseases, i.e. the transmural inflammation of Crohn’s disease (CD) and the inflammation restricted to the colonic mucosa in ulcerative colitis (UC) infiltrations of the plexus by immune cells occur. However, the type of immune cells involved is so far unknown. Therefore, we characterised the immune cell infiltrations of myenteric plexus (MP) in CD and UC compared with controls. Methods We identified 12 IBD patients (four CD and eight UC) and four controls that had received surgery (ileocecal resections or colectomy). The severity of the disease was assessed by Mayo score, HBI score and questionnaires (Visual Analogue Scale, Pain Catastrophizing Scale, Inflammatory bowel disease quality of life and Irritable Bowel Symptom Severity Scale). Formalin-fixed, paraffin-embedded tissue was stained by classical immunohistochemistry. To identify myenteric plexus tissue was stained for CGRP and PGP9.5. Immunostainings for immune cells (T cells: CD3, CD4, CD8, Foxp3; B cells: CD20; monocytes/macrophages: CD68 and CD163) were analysed by quantifying within the plexus and within a defined area of 100 µm around the plexus. Results The mean size of myenteric ganglia in controls was found to be 0.100 ± 0.004 mm² and was significantly decreased in CD (0.055 ± 0.002 mm²) and UC (0.079 ± 0.004 mm²). The population of CD4+ T-cells, macrophages and monocytes within ganglia of the MP were unchanged in CD, UC. However, infiltrates within and around MP contained significantly more CD3+ T cells in CD (121 ± 63 intraganglionic cells/mm² and 1858 ± 1133 periganglionic cells/mm²) and UC (133 ± 80 intraganglionic cells/mm² and 1198 ± 693 periganglionic cells/mm²) compared with controls (28 ± 38 intraganglionic cells/mm² and 342 ± 93 periganglionic cells/mm²). This appeared to be secondary to a significant increase of periganglionic CD8+ T cells in UC (342 ± 293 cells/mm² compared with 164 ± 140 cells/mm² in controls) (see Figure 1) and secondary to a significant increase of periganglionic Foxp3+ T cells in CD (528 ± 193 cells/mm² compared with 0 ± 0 cells/mm² in controls). Moreover, CD20+ B cells were significantly increased in CD (528 ± 193 periganglionic cells/mm² compared with 0 ± 0 periganglionic cells/mm² in controls). Conclusion The intra- and periganglionic infiltrate of MP in inflammatory bowel disease contains CD3+CD8+ T cells in UC and CD3+Foxp3+ regulatory T cells as well as B cells in CD.

OP34 Whole blood profiling of T-cell-derived miRNA allows the development of prognostic models in inflammatory bowel disease

2020 ◽  
Vol 14 (Supplement_1) ◽  
pp. S034-S036
Author(s):  
R Kalla ◽  
A Adams ◽  
R White ◽  
C Clarke ◽  
A Ivens ◽  
...  
Keyword(s):  
Inflammatory Bowel Disease ◽  
T Cells ◽  
T Cell ◽  
Cd8 T Cells ◽  
Bowel Disease ◽  
Whole Blood ◽  
Cd4 T Cells ◽  
Differentially Expressed ◽  
Inflammatory Bowel ◽  
Treatment Escalation

Abstract Background There is an unmet need for blood-based biomarkers that help predict disease and its course at inception to allow tailoring of treatments, achieve early mucosal healing and improve clinical outcomes. In our study, we explore the clinical utility of miRNAs in Inflammatory bowel disease (IBD). Methods A 2-stage prospective multi-centre case–control study was performed. Small RNA sequencing was performed on a discovery cohort of immunomagnetically separated leucocytes (90 CD4+ and CD8+ T-lymphocytes and CD14+ monocytes) from 32 patients (9 CD, 14 UC, 8 healthy controls) to identify differentially expressed cell-specific miRNAs.Top miRNAs were then validated in whole blood in 294 treatment naïve newly diagnosed IBD and non-IBD patients (97 UC, 98 CD, 98 non-IBD) using RT-qPCR, recruited across 5 centres in UK and Europe. Phenotype and outcome data were collected and Cox proportional hazards were derived to assess the contribution of each miRNA to outcomes; defined as the need for 2 or more immunosuppressants and/or surgery after initial disease remission. RT-qPCR target miRNA relative quantification was calculated using 2−ΔΔCq method. Results Each leucocyte subset (30 CD4+ T cells, 28 CD8+ T cells and 32 CD14+ monocytes) was analysed between disease and controls, adjusting for age, gender and batch effects. A total of three miRNAs differentiated IBD from controls in CD4+ T cells including miR-1307-3p (FDR p = 0.01), miR-3615 (p = 0.02) and miR-4792 (p = 0.01); these signals being UC specific. In CD8 T cells, miR-200b-3p was the only differentially expressed miRNA and no CD14+ signals were seen.Three miRNAs were validated in whole blood in an independent multi-centre cohort of 294 patients using RT-qPCR. miR-1307-3p predicted IBD (1.55 fold change (fc),IQR: 1.00–1.87; p = 2.77 × 10–5),in particular UC (1.69 fc, IQR: 1.01–2.00; p = 1.56 × 10–6). Similarly, miR-3615 and miR-4792 were up-regulated in UC compared with controls (1.21fc, IQR:0.91–1.48; p = 8.26 × 10−4and 1.91 fc, IQR: 0.81–2.56; p = 9.21 × 10–3, respectively).There was no correlation with conventional inflammatory markers. Follow-up data were available on 195 IBD patients of which 80 patients required treatment escalation over a median time of 371 days (IQR: 140–711). miR-1307-3p was able to predict disease course in IBD (HR 1.98, IQR: 1.20–3.27; log-rank p = 1.80 × 10−3), in particular CD (HR 2.81; IQR: 1.11–3.53, p = 6.50 × 10–4). In UC, both miR-3615 (HR 3.34, CI: 1.43–7.78, p = 0.01) and miR-4792 (HR 3.96, CI: 1.65–9.52; p = 2.11 × 10–3) predicted treatment escalation. Conclusion We have identified unique CD4+ T-cell miRNAs that are differentially regulated in IBD. These blood-based miRNAs are able to predict treatment escalation at disease inception and have the potential for clinical translation.

Vitamin D Inhibits Pro-Inflammatory T Cell Function in Patients With Inflammatory Bowel Disease

2019 ◽  
Vol 13 (12) ◽  
pp. 1546-1557 ◽  
Author(s):  
Josefine Schardey ◽  
Anna-Maria Globig ◽  
Christine Janssen ◽  
Maike Hofmann ◽  
Philipp Manegold ◽  
...  
Keyword(s):  
Inflammatory Bowel Disease ◽  
Vitamin D ◽  
T Cells ◽  
T Cell ◽  
Cd8 T Cells ◽  
Bowel Disease ◽  
T Cell Subsets ◽  
Cell Phenotype ◽  
Inflammatory Bowel

Abstract Background and Aims Dysregulated T cell responses contribute to the pathogenesis of inflammatory bowel disease [IBD]. Because vitamin D [vitD] deficiency is a risk factor for adverse disease outcomes, we aimed to characterize the impact of vitD on intestinal and peripheral T cell profiles. Methods T cells were isolated from peripheral blood and intestinal biopsies of IBD patients, incubated with vitD and characterized by flow cytometry. To translate these in vitro findings to the clinic, serum vitD concentrations and clinical outcomes were correlated with T cell phenotype and function in a prospective patient cohort. Results Incubation of peripheral and intestinal T cells with 1,25(OH)2-vitD resulted in strongly reduced frequencies of pro-inflammatory CD4+ and CD8+ T cells producing interferon γ [IFNγ], interleukin-17 [IL-17], IL-22, IL-9 and tumour necrosis factor [TNF]. Univariable analysis of 200 IBD patients revealed associations of vitD deficiency with non-compliant vitD intake, season of the year and anaemia in Crohn’s disease [CD] as well as disease activity in ulcerative colitis [UC]. Ex vivo immunophenotyping revealed that CD4+ and CD8+ T cell subsets were not substantially altered in vitD-deficient vs vitD-sufficient patients while regulatory T cell frequencies were reduced in UC and non-smoking CD patients with vitD deficiency. However, normalization of serum vitD concentrations in previously deficient CD patients resulted in significantly reduced frequencies of CD4+ T cells producing IFNγ, IL-17 and IL-22. Conclusion vitD exerts profound anti-inflammatory effects on peripheral and intestinal CD4+ and CD8+ T cells of IBD patients in vitro and inhibits TH1 and TH17 cytokine production in CD patients in vivo.

scholarly journals Transcription and DNA Methylation Patterns of Blood-Derived CD8+ T Cells Are Associated With Age and Inflammatory Bowel Disease But Do Not Predict Prognosis

2021 ◽  
Vol 160 (1) ◽  
pp. 232-244.e7 ◽  
Author(s):  
Marco Gasparetto ◽  
Felicity Payne ◽  
Komal Nayak ◽  
Judith Kraiczy ◽  
Claire Glemas ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Inflammatory Bowel Disease ◽  
T Cells ◽  
Cd8 T Cells ◽  
Bowel Disease ◽  
Inflammatory Bowel ◽  
Methylation Patterns

GUT-DIRECTED SELF-HYPNOSIS FOR INFLAMMATORY BOWEL DISEASE PROTOCOL: COMPLIMENTARY PSYCHOTHERAPY FOR REMISSION AUGMENTATION, IBS-LIKE SYMPTOMS, AND SURGERY RECOVERY

2021 ◽  
Vol 27 (Supplement_1) ◽  
pp. S53-S53
Author(s):  
Joshua Paulton ◽  
Amanjot Gill ◽  
Joelle Prevost
Keyword(s):  
Inflammatory Bowel Disease ◽  
Stress Response ◽  
Mechanism Of Action ◽  
Bowel Disease ◽  
Relaxation Techniques ◽  
Markers Of Inflammation ◽  
Post Surgery ◽  
Patient Goals ◽  
History Of ◽  
Inflammatory Bowel

Abstract Background Gut-directed hypnosis (GDH) is a complimentary therapy for Inflammatory Bowel Disease (IBD), that can be learnt by patients to practice self-hypnosis. GDH in IBD has augmented remission and improved inflammation. GDH has a history of successful use for Irritable Bowel Syndrome (IBS). In IBD it may also improve IBS-like symptoms in remission and recovery from surgery. GDH is suitable for youth and adult IBD patients. In hypnosis, a relaxed state is inducted then suggestions to subconscious mind processes are made. In IBD, the mechanism of action of GDH is unknown but may influence the disease stress response. Aims Aims are the development of a GDH self-hypnosis protocol for IBD, with appropriate target symptoms. Patients first learn to practice with a clinician, then as complimentary psychotherapy for remission augmentation, IBS-like symptoms, and surgery recovery. Methods GDH is practiced first with a clinician, and then by patients as self-hypnosis (table 1). Patients receive psycho-education on GDH for IBD. Next, appropriate treatment goals are made, based on target symptoms. Relaxation techniques induce patient to a deeply relaxed state. Therapeutic suggestions specific to patient goals are given: verbal suggestions, visualizations, and post-hypnotic suggestions. Suggestions can focus on having a healthy digestive system, inflammation and symptoms reduction, and achievement and sustainment of remission. Patients emerge from hypnosis, are debriefed, and encouraged to practice ongoing self-hypnosis. Results In IBD, GDH self-hypnosis can be learnt from clinicians and practiced by patients as a complimentary therapy. Patients’ achievement and sustainment of remission, with clinical markers of inflammation can be monitored. Patients can monitor subjective improvement of IBS-like symptoms and post surgery, recovery progress can be monitored. Conclusions GDH has a history of use for IBS. In IBD, it has been shown to modulate remission, and may improve IBS-like symptoms, and in surgery recovery. The mechanism of action of GDH in IBD may influence the disease stress response. Clinicians trained in GDH are limited currently. Patients may learn GDH self- hypnosis to as a complimentary psychotherapy.

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