scholarly journals Activation, Deficiency, and Reduced IFN-γ Production of Mucosal-Associated Invariant T Cells in Patients with Inflammatory Bowel Disease

2020 ◽  
Vol 12 (5) ◽  
pp. 422-434
Author(s):  
Jae Kyun Ju ◽  
Young-Nan Cho ◽  
Ki-Jeong Park ◽  
Han Deok Kwak ◽  
Hye-Mi Jin ◽  
...  
Keyword(s):  
Inflammatory Bowel Disease ◽  
T Cells ◽  
Bowel Disease ◽  
Inflammatory Bowel ◽  
Ifn Γ ◽  
Invariant T Cells

scholarly journals Wnt/β-catenin activation epigenetically reprograms Regulatory T cells in IBD and progression to dysplasia.

2020 ◽  
Author(s):  
Fotini Gounari ◽  
Jasmin Quandt ◽  
Stephen Arnovitz ◽  
Leila Haghi ◽  
Janine Woehlk ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Inflammatory Bowel Disease ◽  
T Cells ◽  
Regulatory T Cells ◽  
Functional Diversity ◽  
Bowel Disease ◽  
Elevated Expression ◽  
Inflammatory Bowel ◽  
Ifn Γ ◽  
Accessible Chromatin

Abstract The molecular and functional diversity of regulatory T-cells (Tregs) in health and in disease remains unclear. We previously described in colorectal cancer (CRC) patients a subpopulation of RORγt+ Tregs with elevated expression of β-catenin and pro-inflammatory properties. Here we observed progressive expansion of RORγt+ Tregs in inflammatory bowel disease (IBD) patients during inflammation and early dysplasia. Activating Wnt/β-catenin signaling in human and murine Tregs was sufficient to recapitulate the disease-associated increase in frequencies of RORγt+ Tregs expressing IL-17, IFN-γ, and TNFa. We found that binding of the β-catenin interacting partner, TCF-1, to DNA overlapped with Foxp3 binding at enhancer sites of pro-inflammatory pathway genes. Sustained Wnt/β-catenin activation induced newly accessible chromatin sites in these genes and upregulated their expression. These findings indicate that TCF-1 and Foxp3 together limit the expression of pro-inflammatory genes in Tregs. Activation of ꞵ-catenin signaling interferes with this function and promotes the disease-associated RORγt+ Treg phenotype.

Comprehensive Intestinal T Helper Cell Profiling Reveals Specific Accumulation of IFN-γ+IL-17+Coproducing CD4+ T Cells in Active Inflammatory Bowel Disease

2014 ◽  
Vol 20 (12) ◽  
pp. 2321-2329 ◽  
Author(s):  
Anna-Maria Globig ◽  
Nadine Hennecke ◽  
Bianca Martin ◽  
Maximilian Seidl ◽  
Günther Ruf ◽  
...  
Keyword(s):  
Inflammatory Bowel Disease ◽  
T Cells ◽  
Bowel Disease ◽  
Cd4 T Cells ◽  
T Helper Cell ◽  
Helper Cell ◽  
T Helper ◽  
Specific Accumulation ◽  
Inflammatory Bowel ◽  
Ifn Γ

5-Lipoxygenase-derived lipid mediators are not required for the development of NSAID-induced inflammatory bowel disease in IL-10−/−mice

2008 ◽  
Vol 294 (2) ◽  
pp. G477-G488 ◽  
Author(s):  
Seiko Narushima ◽  
Daniel DiMeo ◽  
Jun Tian ◽  
Juan Zhang ◽  
Dahzi Liu ◽  
...  
Keyword(s):  
Inflammatory Bowel Disease ◽  
T Cells ◽  
Bowel Disease ◽  
Early Time ◽  
Neutrophil Infiltration ◽  
Lipid Mediators ◽  
Colon Tissue ◽  
Nsaid Treatment ◽  
Inflammatory Bowel ◽  
Ifn Γ

Leukotrienes are potent lipid mediators derived from the metabolism of arachidonic acid by the enzyme 5-lipoxygenase (5-LO). Elevated levels of the proinflammatory leukotriene LTB4have been found in preclinical models of inflammatory bowel disease (IBD) as well as in colon tissue from individuals with IBD. We therefore determined the extent to which absence of 5-LO-derived lipid mediators would alter the colitis in IL-10−/−mice, a model of human IBD. IL-10−/−/5-LO−/−mice were generated and were healthy. Absence of 5-LO did not alter the development of spontaneous colitis in IL-10-deficient mice. We then evaluated the extent to which absence of 5-LO would alter the development of NSAID-induced colitis in IL-10−/−mice. Absence of 5-LO did not delay the onset or alter the severity of inflammation in NSAID-treated IL-10−/−mice. At an early time point, 3 days after NSAID treatment was initiated, a qualitative increase in the number of dendritic cells and CD4+T cells was noted in the colons of IL-10−/−/5-LO−/−; however, this difference was no longer present after 14 days of NSAID treatment. Absence of 5-LO did not alter the degree of neutrophil infiltration into the in this model. Absence of 5-LO does not alter the development of IFN-γ producing Th1-type CD4+T cells or IL-17 producing CD4+T cells. Absence of 5-LO-derived mediators did not alter the expression of the adhesion molecules ICAM-1 and P-selectin. Development of colitis in IL-10−/−mice was associated with increased levels of the 5-LO-derived anti-inflammatory lipoxin LXA4. These studies demonstrate that 5-LO-derived leukotrienes are not required for the development or maintenance of spontaneous or NSAID-induced colonic inflammation in IL-10−/−mice.

scholarly journals Human basophils interact with memory T cells to augment Th17 responses

Blood ◽  
2012 ◽  
Vol 120 (24) ◽  
pp. 4761-4771 ◽  
Author(s):  
Keiko Wakahara ◽  
Nobuyasu Baba ◽  
Vu Quang Van ◽  
Philippe Bégin ◽  
Manuel Rubio ◽  
...  
Keyword(s):  
Inflammatory Bowel Disease ◽  
T Cells ◽  
Bowel Disease ◽  
Cd4 T Cells ◽  
Memory T Cells ◽  
Allergic Diseases ◽  
Effector Memory ◽  
Independent Manner ◽  
Inflammatory Bowel ◽  
Ifn Γ

Abstract Basophils are a rare population of granulocytes that have long been associated with IgE-mediated and Th2-associated allergic diseases. However, the role of basophils in Th17 and/or Th1 diseases has not been reported. In the present study, we report that basophils can be detected in the mucosa of Th17-associated lung and inflammatory bowel disease and accumulate in inflamed colons containing large quantities of IL-33. We also demonstrate that circulating basophils increased memory Th17 responses. Accordingly, IL-3– or IL-33–activated basophils amplified IL-17 release in effector memory T cells (TEM), central memory T cells (TCM), and CCR6+ CD4 T cells. More specifically, basophils promoted the emergence of IL-17+IFN-γ− and IL-17+IFN-γ+, but not IL-17−IFN-γ+ CD4 T cells in TEM and TCM. Mechanistic analysis revealed that the enhancing effect of IL-17 production by basophils in TEM involved the ERK1/2 signaling pathway, occurred in a contact-independent manner, and was partially mediated by histamine via H2 and H4 histamine receptors. The results of the present study reveal a previously unknown function for basophils in augmenting Th17 and Th17/Th1 cytokine expression in memory CD4 T cells. Because basophils accumulated in inflamed inflammatory bowel disease tissues, we propose that these cells are key players in chronic inflammatory disorders beyond Th2.

scholarly journals Reduced Numbers and Proapoptotic Features of Mucosal-associated Invariant T Cells as a Characteristic Finding in Patients with Inflammatory Bowel Disease

2015 ◽  
Vol 21 (7) ◽  
pp. 1529-1540 ◽  
Author(s):  
Eitaro Hiejima ◽  
Tomoki Kawai ◽  
Hiroshi Nakase ◽  
Tatsuaki Tsuruyama ◽  
Takeshi Morimoto ◽  
...  
Keyword(s):  
Inflammatory Bowel Disease ◽  
T Cells ◽  
Bowel Disease ◽  
Characteristic Finding ◽  
Inflammatory Bowel ◽  
Invariant T Cells

Mucosal Invariant T cells are Diminished in Very Early-Onset Inflammatory Bowel Disease

2021 ◽  
Vol Publish Ahead of Print ◽  
Author(s):  
Ying Dou ◽  
Kelly Maurer ◽  
Maire Conrad ◽  
Trusha Patel ◽  
Rawan Shraim ◽  
...  
Keyword(s):  
Inflammatory Bowel Disease ◽  
T Cells ◽  
Bowel Disease ◽  
Early Onset ◽  
Inflammatory Bowel ◽  
Invariant T Cells
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