scholarly journals Insulin Signaling in Arthritis

2021 ◽  
Vol 12 ◽  
Author(s):  
Cesare Tripolino ◽  
Jacopo Ciaffi ◽  
Valentina Pucino ◽  
Piero Ruscitti ◽  
Nina van Leeuwen ◽  
...  
Keyword(s):  
Immune Response ◽  
T Cells ◽  
Insulin Signaling ◽  
Inflammatory Diseases ◽  
Cellular Membrane ◽  
Effect Relationship ◽  
Increased Risk ◽  
Environmental Agents ◽  
And Migration ◽  
Effect Of Glucose

Inflammatory arthritis is burdened by an increased risk of metabolic disorders. Cytokines and other mediators in inflammatory diseases lead to insulin resistance, diabetes and hyperlipidemia. Accumulating evidence in the field of immunometabolism suggests that the cause-effect relationship between arthritis and metabolic abnormalities might be bidirectional. Indeed, the immune response can be modulated by various factors such as environmental agents, bacterial products and hormones. Insulin is produced by pancreatic cells and regulates glucose, fat metabolism and cell growth. The action of insulin is mediated through the insulin receptor (IR), localized on the cellular membrane of hepatocytes, myocytes and adipocytes but also on the surface of T cells, macrophages, and dendritic cells. In murine models, the absence of IR in T-cells coincided with reduced cytokine production, proliferation, and migration. In macrophages, defective insulin signaling resulted in enhanced glycolysis affecting the responses to pathogens. In this review, we focalize on the bidirectional cause-effect relationship between impaired insulin signaling and arthritis analyzing how insulin signaling may be involved in the aberrant immune response implicated in arthritis and how inflammatory mediators affect insulin signaling. Finally, the effect of glucose-lowering agents on arthritis was summarized.

scholarly journals Two Distinct Etiologies of Gastric Cancer: Infection and Autoimmunity

2021 ◽  
Vol 9 ◽  
Author(s):  
Stella G. Hoft ◽  
Christine N. Noto ◽  
Richard J. DiPaolo
Keyword(s):  
Gastric Cancer ◽  
T Cells ◽  
Gastric Adenocarcinoma ◽  
Inflammatory Diseases ◽  
The United States ◽  
Autoimmune Gastritis ◽  
Gastric Disease ◽  
Increased Risk ◽  
H Pylori ◽  
Gastrointestinal Ulceration

Gastric cancer is a leading cause of mortality worldwide. The risk of developing gastric adenocarcinoma, which comprises >90% of gastric cancers, is multifactorial, but most associated with Helicobacter pylori infection. Autoimmune gastritis is a chronic autoinflammatory syndrome where self-reactive immune cells are activated by gastric epithelial cell autoantigens. This cause of gastritis is more so associated with the development of neuroendocrine tumors. However, in both autoimmune and infection-induced gastritis, high risk metaplastic lesions develop within the gastric mucosa. This warrants concern for carcinogenesis in both inflammatory settings. There are many similarities and differences in disease progression between these two etiologies of chronic gastritis. Both diseases have an increased risk of gastric adenocarcinoma development, but each have their own unique comorbidities. Autoimmune gastritis is a primary cause of pernicious anemia, whereas chronic infection typically causes gastrointestinal ulceration. Both immune responses are driven by T cells, primarily CD4+ T cells of the IFN-γ producing, Th1 phenotype. Neutrophilic infiltrates help clear H. pylori infection, but neutrophils are not necessarily recruited in the autoimmune setting. There have also been hypotheses that infection with H. pylori initiates autoimmune gastritis, but the literature is far from definitive with evidence of infection-independent autoimmune gastric disease. Gastric cancer incidence is increasing among young women in the United States, a population at higher risk of developing autoimmune disease, and H. pylori infection rates are falling. Therefore, a better understanding of these two chronic inflammatory diseases is needed to identify their roles in initiating gastric cancer.

scholarly journals DISCORDANT RESPONSE OF CD4+ T LYMPHOCYTES TO ANTIRETROVIRAL THERAPY

2019 ◽  
Vol 11 (1) ◽  
pp. 16-30 ◽  
Author(s):  
K. V. Shmagel
Keyword(s):  
Immune Response ◽  
T Cells ◽  
Viral Load ◽  
Immune System ◽  
Antiretroviral Therapy ◽  
T Lymphocytes ◽  
Lymphocyte Proliferation ◽  
Immune Reconstitution ◽  
Cell Counts ◽  
Increased Risk

Antiretroviral therapy (ART) in HIV infected patients generally results in the suppression of viral replication and reconstitution of CD4+ T lymphocytes cell counts. In some patients (about 20%), however, a disturbance in regeneration of immune competent cells with a background of low viral load occurs. The term «immunological nonresponders» has been used to describe this phenomenon. Discordant immune response to antiviral therapy may be caused by increasing of depletion and reducing of production of CD4+ T cells. However, mechanisms for low immune reconstitution are not currently well understood. «Immunological nonresponders» exhibit booster lymphocyte proliferation, increased immune activation and reducing of CD4+ T lymphocytes survival time in comparison with patients with concordant response to the therapy. Their immune system is characterized by more pronounced aging and exhaustion. This leads to early and frequent manifestation of AIDSrelated diseases. Besides, immunological nonresponders have an increased risk of non-AIDS-related diseases due to pronounced systemic inflammation. The objective of the present review was to highlight the important problem that is rather common on аntiretroviral therapy and to enlist the specialists to the solving of this issue.

scholarly journals Characterization of Mycobacterium tuberculosis-specific Th22 cells and the effect of tuberculosis disease and HIV co-infection

2020 ◽  
Author(s):  
Mohau S. Makatsa ◽  
F. Millicent A. Omondi ◽  
Rubina Bunjun ◽  
Robert J. Wilkinson ◽  
Catherine Riou ◽  
...  
Keyword(s):  
Immune Response ◽  
T Cells ◽  
Mycobacterium Tuberculosis ◽  
Cd4 T Cells ◽  
Th17 Cells ◽  
Latent Tuberculosis ◽  
Th22 Cells ◽  
Distinct Subset ◽  
Increased Risk ◽  
Ifn Γ

ABSTRACTThe development of a highly effective tuberculosis (TB) vaccine is likely dependent on our understanding of what constitutes a protective immune response to TB. Accumulating evidence suggests that CD4+ T cells producing IL-22, a distinct subset termed ‘Th22’ cells, may contribute to protective immunity to TB. Thus, we characterized Mycobacterium tuberculosis (Mtb)-specific Th22 (and Th1 and Th17) cells in 72 individuals with latent tuberculosis infection (LTBI) or TB disease, with and without human immunodeficiency virus (HIV)-1 infection. We investigated the functional properties (IFN-γ, IL-22 and IL-17 production), memory differentiation (CD45RA, CD27 and CCR7) and activation profile (HLA-DR) of Mtb-specific CD4+ T cells. In HIV-uninfected individuals with LTBI, we detected abundant IFN-γ producing CD4+ T cells (median: 0.93%) and IL-22-producing CD4+ T cells (median: 0.46%) in response to Mtb. The frequency of IL-17 producing CD4+ T cells was much lower, at a median of 0.06%. Consistent with previous studies, IL-22 was produced by a distinct subset of CD4+ T cells and not co-expressed with IL-17. Mtb-specific IL-22 responses were markedly reduced (median: 0.08%) in individuals with TB disease and HIV co-infection compared to IFN-γ responses. Mtb-specific Th22 cells exhibited a distinct memory and activation phenotype compared to Th1 and Th17 cells. Furthermore, Mtb-specific IL-22 was produced by conventional CD4+ T cells that required T cell receptor (TCR) engagement. In conclusion, we confirm that Th22 cells contribute substantially to the immune response to TB. Depletion of Mtb-specific Th22 cells during HIV co-infection may contribute to increased risk of TB disease.

scholarly journals Maprotiline Prompt the Anti-tumor Effect by Inhibiting the PD-L1 in Mice Burdened Melanoma

2021 ◽  
Author(s):  
Tiesuo Zhao ◽  
Yang Li ◽  
Miaomiao Liu ◽  
Lin Zhou ◽  
Zunge Wu ◽  
...  
Keyword(s):  
Immune Response ◽  
T Cells ◽  
Cell Death ◽  
Programmed Cell Death ◽  
Tumor Tissues ◽  
Programmed Cell Death 1 ◽  
Tetracyclic Antidepressant ◽  
And Migration ◽  
Cell Death Protein

Abstract Programmed cell death 1 ligand 1(PD-L1) binds with programmed cell death protein 1 (PD-1) to inhibit the responses of T cells. PD-L1 is significantly upregulated on tumor cells and blocking the PD-L1/PD-1 signal has become an important target of immunotherapy in clinic. At present, some old drugs of non-antitumor have been found that could play the effect of anti-tumor. Maprotiline, as a tetracyclic antidepressant, has been widely used for treating mental depression. Here, we study the anti-tumor effect of maprotiline by strengthening the immune response of mice. In vitro, treatment with maprotiline inhibits the proliferation and migration of B16 cells, increases the cell apoptosis. Importantly, treatment with maprotiline reduces the expression of PD-L1 in tumor tissue, prompts the ratios of CD4+ T cells, CD8+ T cells and NK cells in spleens, increases the infiltration of CD4+ and CD8+ T cells in tumor-tissues. In brief, we determine that maprotiline could prompt the anti-tumor immune response by inhibiting the PD-L1 in mice. This study may find a new inhibitor of PD-L1, which provides a new drug treated tumor in clinical.

scholarly journals Allostatic stress load and CMV serostatus impact immune response to maximal exercise in collegiate swimmers

2020 ◽  
Vol 128 (1) ◽  
pp. 178-188
Author(s):  
Bailey Theall ◽  
Haoyan Wang ◽  
Connor A. Kuremsky ◽  
Eunhan Cho ◽  
Katelyn Hardin ◽  
...  
Keyword(s):  
Immune Response ◽  
T Cells ◽  
B Cell ◽  
Cd8 T Cells ◽  
Maximal Exercise ◽  
Nk Cell ◽  
Stress Load ◽  
Increased Risk ◽  
The Impact ◽  
Time Point

Collegiate athletes are exposed to varying levels of academic and physical stressors, placing them at increased risk for stress-activated latent viral infections. However, the impact of allostatic stress load on the immune response to maximal exercise in athletes remains largely unknown. This study examined the effects of a 7-mo training period and cytomegalovirus (CMV) serostatus on immune cell response to high-intensity swim tests within a group of collegiate swimmers. Samples were collected from 15 National Collegiate Athletic Association Division I swimmers (9 men, 6 women: 19.87 ± 0.64 yr) before and after exhaustive in-pool swims at 2 time points (V1: immediately post-season 1 and V3: beginning of season 2). An additional off-season (V2) time point was collected in a subset of 9 swimmers. Natural killer (NK) cell, B cell, and T cells were quantified by flow cytometry. Linear mixed models were used to determine the effects of exercise, time point, and CMV serostatus (α = 0.05). Resting senescent CD8+ T cells were higher in CMV-seropositive participants at V3 ( P = 0.005). CMV-seronegative participants had a decrease in resting senescent CD8+ T cells from V1 to V3 ( P = 0.021). After acute exercise, CMV-seropositive participants had lower naïve CD8+ T cells ( P < 0.001) and higher senescent CD8+ T cells ( P < 0.001). Increased cumulative stress levels did not appear to affect B-cell and NK-cell compartments. Immune response to exercise was impacted by CMV serostatus and allostatic stress load. Young CMV-seropositive athletes exposed to elevated stressors should be monitored to determine long-term effects of training and academic stressors. NEW & NOTEWORTHY Allostatic stress load is associated with impaired immune response to maximal exercise in cytomegalovirus (CMV)-seropositive subjects but not in CMV-seronegative young healthy adults.

scholarly journals Could the candidate causal gene (LZTFL1) identified by Oxford University scientists, which doubles the risk of COVID-19-related respiratory failure, be used to boost the Weak immunogenicity of COVID-19 mRNA vaccines in patients with B-cell chronic lymphocytic leukemia (CLL)???. A double edged sword

2021 ◽  
Author(s):  
Mahmoud Ramadan Elkazzaz ◽  
Yousry Esam-Eldin Abo-Amer ◽  
Tamer Haydara ◽  
Aziz Rodan Sarohan ◽  
Amr Ahmed
Keyword(s):  
Immune Response ◽  
T Cells ◽  
Retinoic Acid ◽  
Chronic Lymphocytic Leukemia ◽  
B Cell ◽  
Risk Allele ◽  
Lymphocytic Leukemia ◽  
Trans Retinoic Acid ◽  
Increased Risk ◽  
Cell Chronic Lymphocytic Leukemia

Abstract Patients with B-cell chronic lymphocytic leukemia (CLL) have an increased risk of severe infections due to disease- and treatment-related immunodeficiency. As a result, patients with hematologic malignancies have been given priority for primary COVID-19 vaccination. Unfortunately, many studies have suggested that patients with B-cell chronic lymphocytic leukemia (CLL) who have been fully vaccinated can develop severe and often fatal complications. Therefore, adjuvants that can induce mRNA vaccine efficacy are desperately needed for this category of patients with haematological malignancies. A recent, study by Oxford University scientists showed that leucine zipper transcription factor-like 1(LZTFL1), as a candidate causal gene and its enhancer the rs17713054 A risk allele was significantly responsible for the twofold increased risk of respiratory failure from COVID-19 associated with 3p21.31.By using sequence analysis, the risk allele generates a second CCAAT/enhancer binding protein beta (CEBPB) motif in the enhancer. Moreover, neither LZTFL1 variants found in T cells nor B cells are responsible for increasing death risk from COVID-19 infection according to oxford study. Here, we propose attestable hypothesis that trans retinoic acid could enhance the immune response in vaccinated patients with B-cell chronic lymphocytic leukemia (CLL) according to the recent findings of Oxford scientists by inducing the casual gene(LZTFL1) in CD4 T cells and inhibiting (CEBPB) motif.Conclusions Haematological malignancies (blood cancers) patients are more vulnerable to COVID-19 disuse severity and mortality. Un fortunately mRNA vaccine seem to be less effective with weak immune response and insufficient level of generated antibodies in this category of patients. Therefore we suggest all trans retinoic acid is a good candidate as mRNA COVID-19 vaccine adjuvant via inducing LZTFL1 gene in CD4Tcells and this activation could improve the immune response and increase the level of the generated antibodies. Moreover LZTFL1 gene in CD4 T cells is not associated with increasing risk of COVID-19 infection because of absence of its enhancer(The risk allele of the SNP, rs17713054 A) in immune cells according to oxford recent study. In addition to all trans retinoic acid could inhibit CCAAT/enhancer binding protein beta motif that is generated by The risk allele of the SNP, rs17713054 A

scholarly journals Association of Cytomegalovirus DNA and Immunologic Markers of Cardiovascular Disease

2019 ◽  
Vol 6 (5) ◽  
Author(s):  
Ankita Garg ◽  
Sara Gianella ◽  
Masato Nakazawa ◽  
Rodney Trout ◽  
Stephen A Spector
Keyword(s):  
Cardiovascular Disease ◽  
T Cells ◽  
Inflammatory Diseases ◽  
Peripheral Blood Mononuclear ◽  
Hiv Rna ◽  
Immunologic Markers ◽  
Increased Risk ◽  
Ifn Γ ◽  
Circulating T Cells ◽  
Over Time

Abstract Background Persons living with human immunodeficiency virus (HIV) (PLWH) with high cytomegalovirus (CMV)–specific interferon (IFN) γ response have increased numbers of endothelium homing receptor (CX3CR1)+–expressing cells that are associated with cardiovascular disease. The current study was performed to investigate the effect of cellular levels of CMV DNA on these markers. Methods Eighty paired peripheral blood mononuclear cell samples were collected ≥12 months apart from 40 CMV-seropositive PLWH with suppressed HIV RNA, who started antiretroviral therapy at median of 3-months of infection. The samples were assessed for CMV-specific IFN-γ response by means of enzyme-linked immunospot assay, and participants were classified as low responders (LRs) or high responders (HRs) based on IFN-γ production (≤100 or &gt;100 spot-forming units [SFUs]/105 cells). Results Of the 40 participants, 26 (65%) were HRs and 14 (35%) LRs at baseline, which did not change over time or by CMV levels (median at first/second time points, 383/308 SFUs/106 cells for HRs vs 21/41 SFUs/106 for LRs). A decrease in IFN-γ over time was associated with higher CMV DNA levels (P &lt; .01). High CMV response was also associated with increased CD28+CD27−CD4+ T cells expressing CX3CR1 (P &lt; .001). Similarly, increased IFN-γ production was associated with increased CMV-specific CX3CR1+CD28+CD27−CD4+ and CD8+ T cells (P &lt; .001). Conclusions These findings demonstrate that levels of CMV-specific IFN-γ response in PLWH are stable over time, and that HRs have increased circulating T cells expressing CX3CR1 that may put them at increased risk of cardiovascular disease and other inflammatory diseases.

scholarly journals Obesity Challenge Drives Distinct Maternal Immune Response Changes in Normal Pregnant and Abortion-Prone Mouse Models

2021 ◽  
Vol 12 ◽  
Author(s):  
Yanhong Li ◽  
Jiajia Chen ◽  
Yikong Lin ◽  
Ling Xu ◽  
Yifei Sang ◽  
...  
Keyword(s):  
Immune Response ◽  
T Cells ◽  
Nk Cells ◽  
Spontaneous Abortion ◽  
Immune Status ◽  
Normal Pregnancy ◽  
Reproductive Age ◽  
Chow Diet ◽  
Increased Risk ◽  
Maternal Immune Response

Obesity is prevalent among women of reproductive age and is associated with increased risk of developing multiple pregnancy disorders. Pregnancy must induce immune tolerance to avoid fetal rejection, while obesity can cause chronic inflammation through activating the immune system. Impaired maternal immuno-tolerance leads to pregnancy failure, such as recurrent spontaneous abortion (RSA), one of the most common complications during early pregnancy. How does maternal immune response change under obesity stress in normal pregnancy and RSA? In turn, is obesity affected by different gestational statuses? Limited information is presently available now. Our study investigated pregnancy outcomes and maternal immune responses in two murine models (normal pregnancy and spontaneous abortion models) after obesity challenge with a high-fat diet (HFD). Abortion-prone mice fed HFD had significantly higher weight gains during pregnancy than normal pregnant mice with HFD feeding. Nonetheless, the embryo implantation and resorption rates were comparable between HFD and normal chow diet (NCD)-fed mice in each model. Evaluation of immune cell subsets showed HFD-induced obesity drove the upregulation of activated NK cell-activating receptor (NKp46)+ NK cells and pro-inflammatory macrophages (MHCIIhigh Mφ) as well as CD4+ and CD8+ T cells in the normal pregnancy group. However, in the abortion-prone group, relative more immature NK cells with decreased activity phenotypes were found in obese mice. Moreover, there were increased DCreg (CD11bhigh DC) cells and decreased CD4+ and CD8+ T cells detected in the HFD abortion-prone mice relative to those fed the NCD diet. Our findings reveal how pregnancy obesity and maternal immune regulation are mutually influenced. It is worth noting that the abortion-prone model where active maternal immune status was intensified by obesity, in turn stimulated an overcompensation response, leading to an over-tolerized immune status, and predisposing to potential risks of perinatal complications.

scholarly journals Could the candidate causal gene (LZTFL1) identified by Oxford University scientists, which doubles the risk of COVID-19-related respiratory failure, be used to boost the Weak immunogenicity of COVID-19 mRNA vaccines in patients with B-cell chronic lymphocytic leukemia (CLL)???. A double edged sward

2021 ◽  
Author(s):  
Mahmoud Ramadan Elkazzaz ◽  
Yousry Esam-Eldin Abo-Amer ◽  
Amr Ahmed ◽  
Tamer Haydara
Keyword(s):  
Immune Response ◽  
T Cells ◽  
Retinoic Acid ◽  
Chronic Lymphocytic Leukemia ◽  
B Cell ◽  
Risk Allele ◽  
Lymphocytic Leukemia ◽  
Trans Retinoic Acid ◽  
Increased Risk ◽  
Cell Chronic Lymphocytic Leukemia

Abstract Patients with B-cell chronic lymphocytic leukemia (CLL) have an increased risk of severe infections due to disease- and treatment-related immunodeficiency. As a result, patients with hematologic malignancies have been given priority for primary COVID-19 vaccination. Unfortunately, many studies have suggested that patients with B-cell chronic lymphocytic leukemia (CLL) who have been fully vaccinated can develop severe and often fatal complications. Therefore, adjuvants that can induce mRNA vaccine efficacy are desperately needed for this category of patients with haematological malignancies. A recent, study by Oxford University scientists showed that leucine zipper transcription factor-like 1(LZTFL1), as a candidate causal gene and its enhancer the rs17713054 A risk allele was significantly responsible for the twofold increased risk of respiratory failure from COVID-19 associated with 3p21.31.By using sequence analysis, the risk allele generates a second CCAAT/enhancer binding protein beta (CEBPB) motif in the enhancer. Moreover, neither LZTFL1 variants found in T cells nor B cells are responsible for increasing death risk from COVID-19 infection according to oxford study. Here, we propose attestable hypothesis that trans retinoic acid could enhance the immune response in vaccinated patients with B-cell chronic lymphocytic leukemia (CLL) according to the recent findings of Oxford scientists by inducing the casual gene(LZTFL1) in CD4 T cells and inhibiting (CEBPB) motif.Conclusions Haematological malignancies (blood cancers) patients are more vulnerable to COVID-19 disuse severity and mortality. Un fortunately mRNA vaccine seem to be less effective with weak immune response and insufficient level of generated antibodies in this category of patients. Therefore we suggest all trans retinoic acid is a good candidate as mRNA COVID-19 vaccine adjuvant via inducing LZTFL1 gene in CD4Tcells and this activation could improve the immune response and increase the level of the generated antibodies. Moreover LZTFL1 gene in CD4 T cells is not associated with increasing risk of COVID-19 infection because of absence of its enhancer(The risk allele of the SNP, rs17713054 A) in immune cells according to oxford recent study. In addition to all trans retinoic acid could inhibit CCAAT/enhancer binding protein beta motif that is generated by The risk allele of the SNP, rs17713054 A

scholarly journals GAS6 signaling tempers Th17 development in patients with multiple sclerosis and helminth infection

2020 ◽  
Vol 16 (12) ◽  
pp. e1009176
Author(s):  
Juan M. Ortiz Wilczyñski ◽  
Cinthia M. Olexen ◽  
Andrea E. Errasti ◽  
Mirta Schattner ◽  
Carla V. Rothlin ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Immune Response ◽  
T Cells ◽  
Inflammatory Diseases ◽  
Critical Role ◽  
Gene Expression Signature ◽  
Helminth Infections ◽  
Tam Receptors ◽  
Autoimmune Condition ◽  
Antigen Presenting

Multiple sclerosis (MS) is a highly disabling neurodegenerative autoimmune condition in which an unbalanced immune response plays a critical role. Although the mechanisms remain poorly defined, helminth infections are known to modulate the severity and progression of chronic inflammatory diseases. The tyrosine kinase receptors TYRO3, AXL, and MERTK (TAM) have been described as inhibitors of the immune response in various inflammatory settings. We show here that patients with concurrent natural helminth infections and MS condition (HIMS) had an increased expression of the negative regulatory TAM receptors in antigen-presenting cells and their agonist GAS6 in circulating CD11bhigh and CD4+ T cells compared to patients with only MS. The Th17 subset was reduced in patients with HIMS with a subsequent downregulation of its pathogenic genetic program. Moreover, these CD4+ T cells promoted lower levels of the co-stimulatory molecules CD80, CD86, and CD40 on dendritic cells compared with CD4+ T cells from patients with MS, an effect that was GAS6-dependent. IL-10+ cells from patients with HIMS showed higher GAS6 expression levels than Th17 cells, and inhibition of phosphatidylserine/GAS6 binding led to an expansion of Th17 effector genes. The addition of GAS6 on activated CD4+ T cells from patients with MS restrains the Th17 gene expression signature. This cohort of patients with HIMS unravels a promising regulatory mechanism to dampen the Th17 inflammatory response in autoimmunity.

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