scholarly journals Helicobacter pylori-induced REDD1 modulates Th17 cell responses that contributes to gastritis

2021 ◽  
Author(s):  
Zong-Bao Yan ◽  
Jin-Yu Zhang ◽  
Yi-Pin Lv ◽  
Wen-Qing  Tian ◽  
Zhi-Guo Shan ◽  
...  
Keyword(s):  
Th17 Cell ◽  
Cell Polarization ◽  
Cell Responses ◽  
Regulation Function ◽  
H Pylori ◽  
And Function ◽  
Cd4 Cell ◽  
Dependent Pathway ◽  
Wild Type Control ◽  
Inflammatory Effect

Objective: Regulated in development and DNA damage responses-1 (REDD1) is a conserved and ubiquitous protein, which is induced in response to multiple stimuli. However, the regulation, function and clinical relevance of REDD1 in H. pylori-associated gastritis are presently unknown.Approach: Immunohistochemistry, real-time PCR and western blot analyses were performed to examine the levels of REDD1 in gastric samples from H. pylori-infected patients and mice. Gastric tissues from Redd1-/- and wild-type (control) mice were examined for inflammation. Gastric epithelial cells (GECs), monocytes and T cells were isolated, stimulated and/or cultured for REDD1 regulation and function assays.Results: REDD1 was increased in gastric mucosa of H. pylori-infected patients and mice. H. pylori induced GECs to express REDD1 via the phosphorylated cagA that activated MAPKp38 pathway to mediate NF-κB directly binding to REDD1 promoter. Human gastric REDD1 increased with the severity of gastritis, and mouse REDD1 from non-marrow chimera-derived cells promoted gastric inflammation that was characterized by the influx of MHCII+ monocytes. Importantly, gastric inflammation, MHCII+ monocyte infiltration, IL-23 and IL-17A were attenuated in Redd1-/- mice. Mechanistically, REDD1 in GECs regulated CXCL1 production, which attracted MHCII+ monocytes migration by CXCL1-CXCR2 axis. Then H. pylori induced MHCII+ monocytes to secrete IL-23, which favored IL-17A-producing CD4+ cell (Th17 cell) polarization, thereby contributing to the development of H. pylori-associated gastritis.Conclusions: This study identifies a novel regulatory network involving REDD1, which collectively exert a pro-inflammatory effect within gastric microenvironment. Efforts to inhibit this REDD1-dependent pathway may prove valuable strategies in treating of H. pylori-associated gastritis.

Myeloid-derived suppressor cells contribute to systemic lupus erythaematosus by regulating differentiation of Th17 cells and Tregs

2016 ◽  
Vol 130 (16) ◽  
pp. 1453-1467 ◽  
Author(s):  
Jianjian Ji ◽  
Jingjing Xu ◽  
Shuli Zhao ◽  
Fei Liu ◽  
Jingjing Qi ◽  
...  
Keyword(s):  
Disease Activity ◽  
Th17 Cell ◽  
Th17 Cells ◽  
Suppressor Cells ◽  
Cell Polarization ◽  
High Disease Activity ◽  
Myeloid Derived Suppressor Cells ◽  
Systemic Lupus ◽  
And Function

Although major advancements have made in investigating the aetiology of SLE (systemic lupus erythaematosus), the role of MDSCs (myeloid-derived suppressor cells) in SLE progression remains confused. Recently, some studies have revealed that MDSCs play an important role in lupus mice. However, the proportion and function of MDSCs in lupus mice and SLE patients are still poorly understood. In the present study, we investigated the proportion and function of MDSCs using different stages of MRL/lpr lupus mice and specimens from SLE patients with different activity. Results showed that splenic granulocytic (G-)MDSCs were significantly expanded by increasing the expression of CCR1 (CC chemokine receptor 1) in diseased MRL/lpr lupus mice and in high-disease-activity SLE patients. However, the proportion of monocytic (M-)MDSCs remains similar in MRL/lpr lupus mice and SLE patients. G-MDSCs produce high levels of ROS (reactive oxygen species) through increasing gp91phox expression, and activated TLR2 (Toll-like receptor 2) and AIM2 (absent in melanoma 2) inflammasome in M-MDSCs lead to IL-1β (interleukin 1β) expression in diseased MRL/lpr mice and high-disease-activity SLE patients. Previous study has revealed that MDSCs could alter the plasticity of Th17 (T helper 17) cells and Tregs (regulatory T-cells) via ROS and IL-1β. Co-culture experiments showed that G-MDSCs impaired Treg differentiation via ROS and M-MDSCs promoted Th17 cell polarization by IL-1β in vitro. Furthermore, adoptive transfer or antibody depletion of MDSCs in MRL/lpr mice confirmed that MDSCs influenced the imbalance of Tregs and Th17 cells in vivo. Our results indicate that MDSCs with the capacity to regulate Th17 cell/Treg balance may be a critical pathogenic factor in SLE.

scholarly journals Microbiota Metabolite Butyrate Differentially Regulates Th1 and Th17 Cells’ Differentiation and Function in Induction of Colitis

2019 ◽  
Vol 25 (9) ◽  
pp. 1450-1461 ◽  
Author(s):  
Liang Chen ◽  
Mingming Sun ◽  
Wei Wu ◽  
Wenjing Yang ◽  
Xiangsheng Huang ◽  
...  
Keyword(s):  
T Cells ◽  
Cell Differentiation ◽  
T Cell ◽  
Gut Microbiota ◽  
Th17 Cell ◽  
Cell Development ◽  
Cell Polarization ◽  
T Cell Differentiation ◽  
Th1 Cell ◽  
And Function

Abstract Background How the gut microbiota regulates intestinal homeostasis is not completely clear. Gut microbiota metabolite short-chain fatty acids (SCFAs) have been reported to regulate T-cell differentiation. However, the mechanisms underlying SCFA regulation of T-cell differentiation and function remain to be investigated. Methods CBir1, an immunodominant microbiota antigen, transgenic T cells were treated with butyrate under various T-cell polarization conditions to investigate butyrate regulation of T-cell differentiation and the mechanism involved. Transfer of butyrate-treated CBir T cells into Rag1-/- mice was performed to study the in vivo role of such T cells in inducing colitis. Results Although butyrate promoted Th1 cell development by promoting IFN-γ and T-bet expression, it inhibited Th17 cell development by suppressing IL-17, Rorα, and Rorγt expression. Interestingly, butyrate upregulated IL-10 production in T cells both under Th1 and Th17 cell conditions. Furthermore, butyrate induced T-cell B-lymphocyte-induced maturation protein 1 (Blimp1) expression, and deficiency of Blimp1 in T cells impaired the butyrate upregulation of IL-10 production, indicating that butyrate promotes T-cell IL-10 production at least partially through Blimp1. Rag1-/- mice transferred with butyrate-treated T cells demonstrated less severe colitis, compared with transfer of untreated T cells, and administration of anti-IL-10R antibody exacerbated colitis development in Rag-/- mice that had received butyrate-treated T cells. Mechanistically, the effects of butyrate on the development of Th1 cells was through inhibition of histone deacetylase but was independent of GPR43. Conclusions These data indicate that butyrate controls the capacity of T cells in the induction of colitis by differentially regulating Th1 and Th17 cell differentiation and promoting IL-10 production, providing insights into butyrate as a potential therapeutic for the treatment of inflammatory bowel disease.

scholarly journals Viability and Functional Activity of Cryopreserved Mononuclear Cells

2000 ◽  
Vol 7 (4) ◽  
pp. 714-716 ◽  
Author(s):  
Adriana Weinberg ◽  
Li Zhang ◽  
Darby Brown ◽  
Alejo Erice ◽  
Bruce Polsky ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Functional Activity ◽  
Lymphocyte Proliferation ◽  
Mononuclear Cells ◽  
Cell Number ◽  
Peripheral Blood Mononuclear ◽  
Blood Mononuclear Cells ◽  
And Function ◽  
Functional Analyses ◽  
Cd4 Cell

ABSTRACT Factors that influence viability and function of cryopreserved peripheral blood mononuclear cells (PBMC) were identified on 54 samples from 27 AIDS Clinical Trial Units. PBMC viability ranged from 1 to 96% with a median of 70%, was higher in laboratories with experienced staff, and was not significantly associated with CD4 cell number. Function of cryopreserved PBMC, measured by lymphocyte proliferation, was associated with viability. Preparations with viability greater than or equal to 70% had consistent proliferative responses and were suitable for functional analyses.

scholarly journals Gut symbiotic microbes imprint intestinal immune cells with the innate receptor SLAMF4 which contributes to gut immune protection against enteric pathogens

Gut ◽  
2017 ◽  
Vol 67 (5) ◽  
pp. 847-859 ◽  
Author(s):  
Allison Cabinian ◽  
Daniel Sinsimer ◽  
May Tang ◽  
Youngsoon Jang ◽  
Bongkum Choi ◽  
...  
Keyword(s):  
Gut Microbiota ◽  
Immune Cells ◽  
Immune Cell ◽  
Lymphocyte Activation ◽  
Premature Death ◽  
Enteric Pathogens ◽  
Immune Protection ◽  
Intestinal Immunity ◽  
Cell Responses ◽  
And Function

BackgroundInteractions between host immune cells and gut microbiota are crucial for the integrity and function of the intestine. How these interactions regulate immune cell responses in the intestine remains a major gap in the field.AimWe have identified the signalling lymphocyte activation molecule family member 4 (SLAMF4) as an immunomodulator of the intestinal immunity. The aim is to determine how SLAMF4 is acquired in the gut and what its contribution to intestinal immunity is.MethodsExpression of SLAMF4 was assessed in mice and humans. The mechanism of induction was studied using GFPtg bone marrow chimaera mice, lymphotoxin α and TNLG8A-deficient mice, as well as gnotobiotic mice. Role in immune protection was revealed using oral infection with Listeria monocytogenes and Cytobacter rodentium.ResultsSLAMF4 is a selective marker of intestinal immune cells of mice and humans. SLAMF4 induction occurs directly in the intestinal mucosa without the involvement of the gut-associated lymphoid tissue. Gut bacterial products, particularly those of gut anaerobes, and gut-resident antigen-presenting cell (APC)TNLG8A are key contributors of SLAMF4 induction in the intestine. Importantly, lack of SLAMF4 expression leads the increased susceptibility of mice to infection by oral pathogens culminating in their premature death.ConclusionsSLAMF4 is a marker of intestinal immune cells which contributes to the protection against enteric pathogens and whose expression is dependent on the presence of the gut microbiota. This discovery provides a possible mechanism for answering the long-standing question of how the intertwining of the host and gut microbial biology regulates immune cell responses in the gut.

scholarly journals Protective Contributions against Invasive Streptococcus pneumoniae Pneumonia of Antibody and Th17-Cell Responses to Nasopharyngeal Colonisation

PLoS ONE ◽  
2011 ◽  
Vol 6 (10) ◽  
pp. e25558 ◽  
Author(s):  
Jonathan M. Cohen ◽  
Suneeta Khandavilli ◽  
Emilie Camberlein ◽  
Catherine Hyams ◽  
Helen E. Baxendale ◽  
...  
Keyword(s):  
Streptococcus Pneumoniae ◽  
Th17 Cell ◽  
Cell Responses

scholarly journals Deaminase-Independent Mode of Antiretroviral Action in Human and Mouse APOBEC3 Proteins

2020 ◽  
Vol 8 (12) ◽  
pp. 1976
Author(s):  
Yoshiyuki Hakata ◽  
Masaaki Miyazawa
Keyword(s):  
Molecular Mechanisms ◽  
Restriction Factors ◽  
Mrna Editing ◽  
Antiviral Function ◽  
Apobec3 Proteins ◽  
And Function ◽  
Editing Enzyme ◽  
Dependent Pathway ◽  
Independent Mode ◽  
Human Apobec3g

Apolipoprotein B mRNA editing enzyme, catalytic polypeptide-like 3 (APOBEC3) proteins (APOBEC3s) are deaminases that convert cytosines to uracils predominantly on a single-stranded DNA, and function as intrinsic restriction factors in the innate immune system to suppress replication of viruses (including retroviruses) and movement of retrotransposons. Enzymatic activity is supposed to be essential for the APOBEC3 antiviral function. However, it is not the only way that APOBEC3s exert their biological function. Since the discovery of human APOBEC3G as a restriction factor for HIV-1, the deaminase-independent mode of action has been observed. At present, it is apparent that both the deaminase-dependent and -independent pathways are tightly involved not only in combating viruses but also in human tumorigenesis. Although the deaminase-dependent pathway has been extensively characterized so far, understanding of the deaminase-independent pathway remains immature. Here, we review existing knowledge regarding the deaminase-independent antiretroviral functions of APOBEC3s and their molecular mechanisms. We also discuss the possible unidentified molecular mechanism for the deaminase-independent antiretroviral function mediated by mouse APOBEC3.

scholarly journals Dynamic structural cell responses in the thymus to acute injury, regeneration, and age

2021 ◽  
Author(s):  
Lorenz L Jahn ◽  
Anastasia I Kousa ◽  
Lisa Sikkema ◽  
Angel E Flores ◽  
Kimon V Argyropoulos ◽  
...  
Keyword(s):  
T Cell ◽  
T Cell Development ◽  
Marrow Transplant ◽  
Cell Development ◽  
Acute Injury ◽  
Thymic Function ◽  
Structural Cell ◽  
Cell Responses ◽  
And Function ◽  
Old Mice

The thymus, the primary site of T cell development, is extremely sensitive to insult but also harbors tremendous capacity for repair. Using single cell sequencing of thymic structural cells, as well as functional and structural analyses, we revealed distinct regenerative programs by endothelial and mesenchymal subsets after injury that stimulated epithelial repair; the compartment primarily supporting T cell development. Thymic function not only declined over lifespan, contributing to immune aging, but the capacity of the thymus to regenerate after damage also declined in old mice. This could be attributed to an inability of the old microenvironment to induce reparative programs; leading to reduced ability to restore tissue structure and function. These findings provide a detailed framework for the response of structural cells to aging and acute damage, which could have considerable implications for our understanding of aging immunity and recovery from treatments such as chemotherapy and bone marrow transplant.

scholarly journals TLR7 modulating B-cell immune responses in the spleen of C57BL/6 mice infected with Schistosoma japonicum

2021 ◽  
Vol 15 (11) ◽  
pp. e0009943
Author(s):  
Haixia Wei ◽  
Hongyan Xie ◽  
Jiale Qu ◽  
Anqi Xie ◽  
Shihao Xie ◽  
...  
Keyword(s):  
B Cells ◽  
B Cell ◽  
Gene Knockout ◽  
Innate Immune ◽  
Wild Type ◽  
Cell Responses ◽  
Splenic Cells ◽  
And Function ◽  
Egg Antigen

B cells played an important role in Schistosoma infection-induced diseases. TLR7 is an intracellular member of the innate immune receptor. The role of TLR7 on B cells mediated immune response is still unclear. Here, C57BL/6 mice were percutaneously infected by S. japonicum for 5–6 weeks. The percentages and numbers of B cells increased in the infected mice (p < 0.05), and many activation and function associated molecules were also changed on B cells. More splenic cells of the infected mice expressed TLR7, and B cells were served as the main cell population. Moreover, a lower level of soluble egg antigen (SEA) specific antibody and less activation associated molecules were found on the surface of splenic B cells from S. japonicum infected TLR7 gene knockout (TLR7 KO) mice compared to infected wild type (WT) mice (p < 0.05). Additionally, SEA showed a little higher ability in inducing the activation of B cells from naive WT mice than TLR7 KO mice (p < 0.05). Finally, the effects of TLR7 on B cells are dependent on the activation of NF-κB p65. Altogether, TLR7 was found modulating the splenic B cell responses in S. japonicum infected C57BL/6 mice.

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