scholarly journals RORγt-Expressing Pathogenic CD4+T Cells Cause Brain Inflammation During Chronic Colitis

2021 ◽  
Author(s):  
Rajatava Basu ◽  
Michel Edwar Mickael ◽  
Suniti Bhaumik ◽  
Ayanabha Chakraborti ◽  
Alan Umfress ◽  
...  
Keyword(s):  
T Cells ◽  
Cd4 T Cells ◽  
Intestinal Inflammation ◽  
Brain Inflammation ◽  
Brain Diseases ◽  
Transfer Model ◽  
Chronic Colitis ◽  
Neurobehavioral Disorders ◽  
Chronic Intestinal Inflammation ◽  
The Brain

Neurobehavioral disorders and brain abnormalities have been extensively reported in both Crohn's Disease (CD) and Ulcerative Colitis (UC) patients. However, the mechanism causing neuropathological disorders in inflammatory bowel disease (IBD) patients remains unknown. Studies have linked the Th17 subset of CD4+T cells to brain diseases associated with neuroinflammation and cognitive impairment, including multiple sclerosis (MS), ischemic brain injury, and Alzheimer's disease. To better understand how CD4+T lymphocytes, contribute to brain pathology in chronic intestinal inflammation, we investigated the development of brain inflammation in the T cell transfer model of chronic colitis. Our findings demonstrate that CD4+T cells infiltrate the brain of colitic Rag1-/- mice in proportional levels to colitis severity. Colitic mice developed hypothalamic astrogliosis that correlated with neurobehavioral disorders. Moreover, the brain-infiltrating CD4+T cells expressed Th17 cell transcription factor RORγt and displayed a pathogenic Th17 cellular phenotype similar to colonic Th17 cells. Adoptive transfer of RORγt-deficient naive CD4+T cells failed to cause brain inflammation and neurobehavioral disorders in Rag1-/- recipients, with significantly less brain infiltration of CD4+T cells. These findings suggest that pathogenic RORγt+CD4+T cells that aggravate colitis migrate preferentially into the brain, contributing to brain inflammation and neurobehavioral disorders, thereby linking colitis severity to neuroinflammation.

Phenotypically distinct subsets of CD4+ T cells induce or protect from chronic intestinal inflammation in C. B-17 scid mice

1993 ◽  
Vol 5 (11) ◽  
pp. 1461-1471 ◽  
Author(s):  
Flona Powrie ◽  
Michael W. Leach ◽  
Smita Mauze ◽  
Linda Barcomb Caddie ◽  
Robert L. Coffman
Keyword(s):  
T Cells ◽  
Cd4 T Cells ◽  
Intestinal Inflammation ◽  
Scid Mice ◽  
Chronic Intestinal Inflammation

scholarly journals Effector CD4 T cells with progenitor potential mediate chronic intestinal inflammation

2018 ◽  
Vol 215 (7) ◽  
pp. 1803-1812 ◽  
Author(s):  
Boyoung Shin ◽  
Robert L. Kress ◽  
Philip A. Kramer ◽  
Victor M. Darley-Usmar ◽  
Susan L. Bellis ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cd4 T Cells ◽  
Intestinal Inflammation ◽  
Gene Signature ◽  
Cell Responses ◽  
Specific Effector ◽  
Discrete Population ◽  
Chronic Intestinal Inflammation ◽  
St6gal I

Dysregulated CD4 T cell responses are causally linked to autoimmune and chronic inflammatory disorders, yet the cellular attributes responsible for maintaining the disease remain poorly understood. Herein, we identify a discrete population of effector CD4 T cells that is able to both sustain and confer intestinal inflammation. This subset of pathogenic CD4 T cells possesses a unique gene signature consistent with self-renewing T cells and hematopoietic progenitor cells, exhibits enhanced survival, and continually seeds the terminally differentiated IFNγ-producing cells in the inflamed intestine. Mechanistically, this population selectively expresses the glycosyltransferase ST6Gal-I, which is required for optimal expression of the stemness-associated molecule TCF1 by effector CD4 T cells. Our findings indicate that the chronicity of T cell–mediated inflammation is perpetuated by specific effector CD4 T cells with stem-like properties.

scholarly journals IL-1β mediates chronic intestinal inflammation by promoting the accumulation of IL-17A secreting innate lymphoid cells and CD4+ Th17 cells

2012 ◽  
Vol 209 (9) ◽  
pp. 1595-1609 ◽  
Author(s):  
Margherita Coccia ◽  
Oliver J. Harrison ◽  
Chris Schiering ◽  
Mark J. Asquith ◽  
Burkhard Becher ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cd4 T Cells ◽  
Intestinal Inflammation ◽  
Inflammatory Responses ◽  
Innate Lymphoid Cells ◽  
Lymphoid Cells ◽  
Intestinal Pathology ◽  
Bowel Diseases ◽  
Chronic Intestinal Inflammation

Although very high levels of interleukin (IL)-1β are present in the intestines of patients suffering from inflammatory bowel diseases (IBD), little is known about the contribution of IL-1β to intestinal pathology. Here, we used two complementary models of chronic intestinal inflammation to address the role of IL-1β in driving innate and adaptive pathology in the intestine. We show that IL-1β promotes innate immune pathology in Helicobacter hepaticus–triggered intestinal inflammation by augmenting the recruitment of granulocytes and the accumulation and activation of innate lymphoid cells (ILCs). Using a T cell transfer colitis model, we demonstrate a key role for T cell–specific IL-1 receptor (IL-1R) signals in the accumulation and survival of pathogenic CD4+ T cells in the colon. Furthermore, we show that IL-1β promotes Th17 responses from CD4+ T cells and ILCs in the intestine, and we describe synergistic interactions between IL-1β and IL-23 signals that sustain innate and adaptive inflammatory responses in the gut. These data identify multiple mechanisms through which IL-1β promotes intestinal pathology and suggest that targeting IL-1β may represent a useful therapeutic approach in IBD.

scholarly journals Antibodies to interleukin 12 abrogate established experimental colitis in mice.

1995 ◽  
Vol 182 (5) ◽  
pp. 1281-1290 ◽  
Author(s):  
M F Neurath ◽  
I Fuss ◽  
B L Kelsall ◽  
E Stüber ◽  
W Strober
Keyword(s):  
T Cells ◽  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Murine Model ◽  
Cd4 T Cells ◽  
Intestinal Inflammation ◽  
Interleukin 12 ◽  
Trinitrobenzene Sulfonic Acid ◽  
Ifn Gamma ◽  
Chronic Intestinal Inflammation

In this study, we describe a novel murine model of chronic intestinal inflammation induced by the hapten reagent 2,4,6-trinitrobenzene sulfonic acid (TNBS). Rectal application of low doses of TNBS in BALB/c and SJL/J mice resulted in a chronic transmural colitis with severe diarrhea, weight loss, and rectal prolapse, an illness that mimics some characteristics of Crohn's disease in humans. The colon of TNBS-treated mice on day 7 was marked by infiltration of CD4+ T cells; furthermore, in situ polymerase chain reaction studies revealed high levels of interferon (IFN)-gamma mRNA in diseased colons. Isolated lamina propria (LP) CD4+ T cells from TNBS-treated mice stimulated with anti-CD3 and anti-CD28 antibodies exhibited a Th1 pattern of cytokine secretion: a 20-50-fold increase in IL-2 and IFN-gamma levels and a 5-fold decrease in IL-4 levels as compared with those of stimulated LP CD4+ T cells from control BALB/c mice. Administration of monoclonal anti-IL-12 antibodies to the TNBS-treated mice both early (at 5 d) and late (at 20 d) after induction of colitis led to a striking improvement in both the clinical and histopathological aspects of the disease and frequently abrogated the established colitis completely. Furthermore, LP CD4+ T cells isolated from anti-IL-12-treated mice failed to secrete IFN-gamma upon in vitro stimulation. In summary, the data demonstrate the pivotal role of IL-12 and IFN-gamma in a TNBS-induced murine model of chronic intestinal inflammation. Furthermore, they suggest the potential utility of anti-IL-12 antibodies in patients with Crohn's disease.

1094 The Impact of HDAC Inhibition On CD4+ T Cells in Chronic Intestinal Inflammation

2009 ◽  
Vol 136 (5) ◽  
pp. A-169
Author(s):  
Rainer Glauben ◽  
Elena Sonnenberg ◽  
Thorsten Stroh ◽  
Inka Fedke ◽  
Paolo Mascagni ◽  
...  
Keyword(s):  
T Cells ◽  
Cd4 T Cells ◽  
Intestinal Inflammation ◽  
Hdac Inhibition ◽  
The Impact ◽  
Chronic Intestinal Inflammation

scholarly journals IL-7 promotes long-term in vitro survival of unique long-lived memory subset generated from mucosal effector memory CD4+ T cells in chronic colitis mice

2013 ◽  
Vol 156 (1-2) ◽  
pp. 82-93 ◽  
Author(s):  
Masahiro Takahara ◽  
Yasuhiro Nemoto ◽  
Shigeru Oshima ◽  
Yu Matsuzawa ◽  
Takanori Kanai ◽  
...  
Keyword(s):  
T Cells ◽  
Cd4 T Cells ◽  
Effector Memory ◽  
Chronic Colitis ◽  
Memory Cd4 T Cells ◽  
In Vitro Survival ◽  
Memory Subset

scholarly journals Berberine improved experimental chronic colitis by regulating interferon-γ- and IL-17A-producing lamina propria CD4+ T cells through AMPK activation

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Masahiro Takahara ◽  
Akinobu Takaki ◽  
Sakiko Hiraoka ◽  
Takuya Adachi ◽  
Yasuyuki Shimomura ◽  
...  
Keyword(s):  
T Cells ◽  
Lamina Propria ◽  
Cd4 T Cells ◽  
Interferon Γ ◽  
Ampk Activation ◽  
Chronic Colitis

scholarly journals Induced Reactivity of Intestinal CD4+ T Cells with an Epithelial Cell Lectin, Galectin-4, Contributes to Exacerbation of Intestinal Inflammation

Immunity ◽  
2004 ◽  
Vol 20 (6) ◽  
pp. 681-693 ◽  
Author(s):  
Akira Hokama ◽  
Emiko Mizoguchi ◽  
Ken Sugimoto ◽  
Yasuyo Shimomura ◽  
Yosuke Tanaka ◽  
...  
Keyword(s):  
T Cells ◽  
Epithelial Cell ◽  
Cd4 T Cells ◽  
Intestinal Inflammation
Sign in / Sign up

Export Citation Format

Share Document