scholarly journals CD4+ CD8αα+ T cells in the gastric epithelium mediate chronic inflammation induced by Helicobacter felis

2021 ◽  
pp. 105151
Author(s):  
Guojing Ruan ◽  
An Huang ◽  
Chupeng Hu ◽  
Ningyin Xu ◽  
Menghui Fan ◽  
...  
Keyword(s):  
T Cells ◽  
Chronic Inflammation ◽  
Gastric Epithelium ◽  
Helicobacter Felis

scholarly journals CD4+ CD8αα+ T Cells in the Gastric epithelium Mediate Chronic Inflammation Induced by Helicobacter Felis

2021 ◽  
Author(s):  
Guojing Ruan ◽  
An Huang ◽  
Chupeng Hu ◽  
Ningyin Xu ◽  
Menghui Fan ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Vaccine Efficacy ◽  
Gastric Epithelium ◽  
Double Positive ◽  
Helicobacter Felis ◽  
Local Immunosuppression ◽  
Infiltrating Lymphocytes

Abstract CD4+ CD8αα+ double-positive intraepithelial T lymphocytes (DP T cells), a newly characterized subset of intraepithelial T cell, has been reported to contribute to local immunosuppression. However, whether DP T cells are present in Helicobacter. pylori-induced gastritis, and their relationship with disease prognosis remain to be elucidated. In this study, We established chronic gastritis models through Helicobacter felis (H. felis) infection. Gastric infiltrating lymphocytes were isolated from H. felis-induced gastritis mice and analyzed by flow cytometry. Our results suggest that DP T cells frequency in H. felis-induced gastritis mice was higher than the uninfected mice. Gastric DP T cells derived from lamina propria cells, which distributed in the gastric epithelial layer. We found that DP T cells exhibited anti-inflammatory function. In vitro, DP T cells inhibited the maturation of dendritic cells and the proliferation of CD4+ T cell. The elimination of CD4+CD8αα+ T cells in vivo resulted in severe gastritis and a reduction of H. felis load. Additionally, vaccine with silk fibroin as delivery systems enhanced vaccine efficacy by reducing DP T cells. We demonstrated that DP T cells performed an immunosuppressive role in Helicobacter felis-induced gastritis. These findings revealed that DP T cells may affect the prognosis of the disease and the vaccine efficacy.

scholarly journals Interleukin 7 Transgenic Mice Develop Chronic Colitis with Decreased Interleukin 7 Protein Accumulation in the Colonic Mucosa

1998 ◽  
Vol 187 (3) ◽  
pp. 389-402 ◽  
Author(s):  
Mamoru Watanabe ◽  
Yoshitaka Ueno ◽  
Tomoharu Yajima ◽  
Susumu Okamoto ◽  
Tatsuhiko Hayashi ◽  
...  
Keyword(s):  
T Cells ◽  
Epithelial Cells ◽  
Transgenic Mice ◽  
Chronic Inflammation ◽  
Colonic Mucosa ◽  
Flow Cytometric Analysis ◽  
Receptor Expression ◽  
Protein Accumulation ◽  
Chronic Colitis ◽  
Interleukin 7

We have demonstrated that intestinal epithelial cells produce interleukin 7 (IL-7), and IL-7 serves as a potent regulatory factor for proliferation of intestinal mucosal lymphocytes expressing functional IL-7 receptor. To clarify the mechanism by which locally produced IL-7 regulates the mucosal lymphocytes, we investigated IL-7 transgenic mice. Here we report that transgenic mice expressing murine IL-7 cDNA driver by the SRα promoter developed chronic colitis in concert with the expression of SRα/IL-7 transgene in the colonic mucosa. IL-7 transgenic but not littermate mice developed chronic colitis at 4–12 wk of age, with histopathological similarity to ulcerative colitis in humans. Southern blot hybridization and competitive PCR demonstrated that the expression of IL-7 messenger RNA was increased in the colonic mucosal lymphocytes but not in the colonic epithelial cells. IL-7 protein accumulation was decreased in the goblet cell–depleted colonic epithelium in the transgenic mice. Immunohistochemical and cytokine production analysis showed that lymphoid infiltrates in the lamina propria were dominated by T helper cell type 1 CD4+ T cells. Flow cytometric analysis demonstrated that CD4+ intraepithelial T cells were increased, but T cell receptor γ/δ T cells and CD8α/α cells were not increased in the area of chronic inflammation. Increased IL-7 receptor expression in mucosal lymphocytes was demonstrated in the transgenic mice. These findings suggest that chronic inflammation in the colonic mucosa may be mediated by dysregulation of colonic epithelial cell–derived IL-7, and this murine model of chronic colitis may contribute to the understanding of the pathogenesis of human inflammatory bowel disease.

Autoimmune hepatitis

2010 ◽  
pp. 2460-2464
Author(s):  
H.J.F. Hodgson
Keyword(s):  
T Cells ◽  
Type 1 Diabetes ◽  
Autoimmune Diseases ◽  
Autoimmune Hepatitis ◽  
Chronic Inflammation ◽  
Case History ◽  
Plasma Cells ◽  
Portal Tract ◽  
History Of

Case History—A 24 yr old woman presenting with a short history of jaundice. Autoimmune hepatitis describes chronic inflammation in the liver attributed to immune responses against self-antigens in the liver, typically in the form of a marked portal tract infiltrate containing both plasma cells and T cells. It usually affects women (female:male, 8:1), is often familial, and 60% of patients have other autoimmune diseases (e.g. thyroiditis, type 1 diabetes) in addition....

scholarly journals Violacein Treatment Modulates Acute and Chronic Inflammation through the Suppression of Cytokine Production and Induction of Regulatory T Cells

PLoS ONE ◽  
2015 ◽  
Vol 10 (5) ◽  
pp. e0125409 ◽  
Author(s):  
Liana Verinaud ◽  
Stefanie Costa Pinto Lopes ◽  
Isabel Cristina Naranjo Prado ◽  
Fábio Zanucoli ◽  
Thiago Alves da Costa ◽  
...  
Keyword(s):  
T Cells ◽  
Regulatory T Cells ◽  
Chronic Inflammation ◽  
Cytokine Production ◽  
Acute And Chronic Inflammation

Immunology

2017 ◽  
Author(s):  
Dennis J. Hartigan-O’Connor ◽  
Christian Brander
Keyword(s):  
T Cells ◽  
Chronic Inflammation ◽  
Cd4 T Cells ◽  
Immune Reconstitution ◽  
Opportunistic Infections ◽  
Cd4 T Cell ◽  
Elite Controllers ◽  
Gastrointestinal Mucosa ◽  
Key Factor ◽  
Hiv Antiretroviral Therapy

The key factor in HIV pathogenesis is the decline in CD4+ T cells with resultant immunodeficiency and chronic inflammation. Depletion of CD4+ T cells from the gastrointestinal mucosa followed by microbial translocation and subsequent immune activation are components of disease progression in untreated patients. Symptomatic and occult opportunistic infections including cytomegalovirus contribute to chronic inflammation in persons infected with HIV. Antiretroviral therapy (ART) results in immune reconstitution, with increases in peripheral CD4+ T cell lymphocytes in most persons infected with HIV, although immune recovery is quite variable. A subset of patients with AIDS will develop immune reconstitution inflammatory syndromes after initiation of ART. Approximately 1% of persons with HIV are able to control infection without the need for ART (“elite” controllers). A variety of immune-based therapies, including hydroxyurea, growth hormone, and statins, are being studied in clinical trials and may ultimately play a role in treating persons with HIV infection.

Dysregulated Interleukin -33/ST2 Pathway Perpetuates Chronic Inflammation in Hashimoto’s Thyroiditis

2019 ◽  
Vol 19 (7) ◽  
pp. 1012-1021 ◽  
Author(s):  
Xuan Wang ◽  
Xiaoqing Shao ◽  
Xinhao Liu ◽  
Qiu Qin ◽  
Jian Xu ◽  
...  
Keyword(s):  
Flow Cytometry ◽  
T Cells ◽  
Western Blot ◽  
Chronic Inflammation ◽  
Hashimoto’S Thyroiditis ◽  
Thyroid Tissue ◽  
Hashimoto's Thyroiditis ◽  
Enzyme Linked Immunosorbent Assay ◽  
Control Group ◽  
Interleukin 33

Objective: Hashimoto’s Thyroiditis (HT) is an autoimmune disease, characterized by chronic inflammation of the thyroid gland with unknown etiologies. Recently, interleukin-33/ST2 (IL- 33/ST2) pathway reveals its participation in the process of several autoimmune diseases. In this study, the role of IL-33/ST2 pathway in the development of HT is investigated. Methods: The levels of plasma IL-33, sST2 and the frequency of circulating CD4+ST2L+T cells in 30 HT patients and 20 healthy controls were determined by enzyme-linked immunosorbent assay (ELISA) and flow cytometry respectively. The mRNA expressions of related molecules in IL-33/ST2 pathway in thyroid tissues (12 HT patients and 10 controls) were detected by real-time quantitative PCR (RTqPCR). The protein expressions of IL-33 and ST2 were determined by Western blot and immunohistochemistry staining. Results: The mRNA expressions of plasma IL-33 and sST2 were elevated in HT patients, with an increased ratio of IL-33/sST2. The number of CD4+ST2L+ T cells in PBMCs of HT group was significantly increased when compared to the control group (CON) by Flow cytometry assay. MRNA Expression of IL-33 and ST2 in thyroid tissue and the level of IL-1β and IL-18 were significantly upregulated in HT patients, while IL-5 was down-regulated in HT patients, compared to CON. The expression of IL-1β and IL-18 were positively correlated with the expression of IL-33. Results of western blot and immunohistochemical staining were consistent with qPCR. Conclusion: IL-33/ST2 pathway participates in HT via affecting the production of inflammatory cytokines.

scholarly journals Role of Immune Cells in Patients with Hepatitis B Virus-Related Hepatocellular Carcinoma

2021 ◽  
Vol 22 (15) ◽  
pp. 8011
Author(s):  
Hyo-Jung Cho ◽  
Jae-Youn Cheong
Keyword(s):  
Hepatocellular Carcinoma ◽  
T Cells ◽  
Hepatitis B Virus ◽  
Hepatitis B ◽  
Chronic Inflammation ◽  
Cd8 T Cells ◽  
Immune Cells ◽  
Adaptive Immune ◽  
B Virus

Hepatocellular carcinoma (HCC) develops almost entirely in the presence of chronic inflammation. Chronic hepatitis B virus (HBV) infection with recurrent immune-mediated liver damage ultimately leads to cirrhosis and HCC. It is widely accepted that HBV infection induces the dysfunction of the innate and adaptive immune responses that engage various immune cells. Natural killer (NK) cells are associated with early antiviral and antitumor properties. On the other hand, inflammatory cells release various cytokines and chemokines that may promote HCC tumorigenesis. Moreover, immunosuppressive cells such as regulatory T cells (Treg) and myeloid-derived suppressive cells play a critical role in hepatocarcinogenesis. HBV-specific CD8+ T cells have been identified as pivotal players in antiviral responses, whilst extremely activated CD8+ T cells induce enormous inflammatory responses, and chronic inflammation can facilitate hepatocarcinogenesis. Controlling and maintaining the balance in the immune system is an important aspect in the management of HBV-related HCC. We conducted a review of the current knowledge on the immunopathogenesis of HBV-induced inflammation and the role of such immune activation in the tumorigenesis of HCC based on the recent studies on innate and adaptive immune cell dysfunction in HBV-related HCC.

The Involvement of STAT/SOCS Signaling in miRNA-Induced T Cell Exhaustion in Cutaneous T-Cell Lymphoma

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 1-1
Author(s):  
Zhen Han ◽  
Chingyu Su ◽  
Renee J. Estephan ◽  
Xiwei Wu ◽  
Sung Hee Kil ◽  
...  
Keyword(s):  
T Cells ◽  
Data Analysis ◽  
T Cell ◽  
Chronic Inflammation ◽  
Cell Lymphoma ◽  
Immune Checkpoints ◽  
T Cell Exhaustion ◽  
Cutaneous T Cell Lymphoma ◽  
Cell Exhaustion ◽  
Qrt Pcr

Background: Cutaneous T-cell lymphoma (CTCL), collectively known as mycosis fungoides (MF) and Sézary syndrome (SS) arises from CD4+ T cells in a background of chronic inflammation. The chronic inflammation fosters the growth of CTCL cells and may facilitate T-cells exhaustion that is characterized by deprived effector function and sustained expression of inhibitory receptors. As a result, malignant CTCL cells escape immune surveillance and are not eliminated. At present, the roles of miRNAs or signaling pathways involved in the expression of immune checkpoints in CTCL has yet to be elucidated. Therefore, this project is aimed to elucidate how immune checkpoints are regulated by miRNAs, and how this regulation contributes to T-cell exhaustion and the development of CTCL. Methods: We first conducted miRNAseq analysis to assess the miRNA profile of 50 CTCL patient tumor samples. The sequencing data analysis was performed at the City of Hope Integrative Genomics Core. Next, we verified the expression of 3 highly upregulated miRNAs (miR-155, -21 and -130) from the miRNAseq analysis in 5 CTCL cell lines and tumor samples using qRT-PCR and in situ hybridization (ISH). Finally, we transfected the CTCL cell line Myla 2059 and HuT 78 with anti-miR-155, -21, -130 or Scramble (Scr) control using the Lonza nucleofection kit and nucleofector machine. Cell lysates were prepared 72 hours after transfection and then subjected to Western Blot analysis. We probed the blot with antibodies against SOCS, PTEN, pSTAT3 and GAPDH as a loading control. Results: The data analysis revealed that miR-155 had the highest correlation with CTLA-4 (r = 0.59, P < 0.0001), PD1 (r = 0.42, P = 0.0021), PD-L1 (r = 0.42, P = 0.0025), TIM3 (r = 0.63, P < 0.0001), LAG3 (r = 0.57, P < 0.0001), and ICOS (r = 0.74, P < 0.0001) mRNA; -21 had the highest correlation with PD-L1 (r = 0.44, P = 0.0012), TIM3 (r = 0.52, P < 0.0001), and ICOS (r = 0.37, P < 0.0073) mRNA; and -130 had the highest correlation with CTLA-4 (r = 0.5, P = 0.0002), PD-L1 (r = 0.54, P < 0.0001), TIM3 (r = 0.69, P < 0.0001), LAG3 (r = 0.49, P = 0.0003), and ICOS (r = 0.68, P < 0.0001) mRNA. qRT-PCR and ISH revealed that miRs-155, -21 and -130 were upregulated in all 5 CTCL cell lines and primary tumor samples. There was a dramatic increase in SOCS proteins and significant decrease in pSTAT3 expression in Myla 2059 and HuT 78 cells transfected with anti-miRs-155, -21 or -130, compared to cells transfected with Scr. Conclusions: Immune checkpoints and ligands like PD-L1 expression in CTCL are regulated by miRs-155, -21 and -130. The SOCS family of proteins, negative regulators of STAT signaling, are involved in miRs-155, -21 and -130-induced immune checkpoints expression in CTCL. Taken together, these results demonstrate the mechanisms of miRNA-induced T cell exhaustion and pave the way for the development of miRNA therapeutics in CTCL. Disclosures Rosen: Seattle Genetics: Consultancy; Celgene: Speakers Bureau; paradigm Medical Communications: Speakers Bureau; Abbvie: Speakers Bureau; NeoGenomics: Consultancy; Aileron Therapeutics: Consultancy; Novartis: Consultancy; Pebromene: Consultancy. Querfeld:Celgene: Research Funding; Stemline: Consultancy; Trillium: Consultancy; MiRagen: Consultancy; Kyowa Kirin: Consultancy; Bioniz: Consultancy; Helsinn: Consultancy.

Free radicals and redox signalling in T-cells during chronic inflammation and ageing

2011 ◽  
Vol 39 (5) ◽  
pp. 1273-1278 ◽  
Author(s):  
Helen R. Griffiths ◽  
Christopher R. Dunston ◽  
Stuart J. Bennett ◽  
Melissa M. Grant ◽  
Darren C. Phillips ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Chronic Inflammation ◽  
Cell Function ◽  
Cell Phenotype ◽  
Cell Functions ◽  
Cytoplasmic Proteins ◽  
Local Cell ◽  
Species Production

During chronic inflammation and ageing, the increase in oxidative stress in both intracellular and extracellular compartments is likely to influence local cell functions. Redox changes alter the T-cell proteome in a quantitative and qualitative manner, and post-translational modifications to surface and cytoplasmic proteins by increased reactive species can influence T-cell function. Previously, we have shown that RA (rheumatoid arthritis) T-cells exhibit reduced ROS (reactive oxygen species) production in response to extracellular stimulation compared with age-matched controls, and basal ROS levels [measured as DCF (2′,7′-dichlorofluorescein) fluorescence] are lower in RA T-cells. In contrast, exposing T-cells in vitro to different extracellular redox environments modulates intracellular signalling and enhances cytokine secretion. Together, these data suggest that a complex relationship exists between intra- and extra-cellular redox compartments which contribute to the T-cell phenotype.

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