scholarly journals TRPA1 Expression and Pathophysiology in Immune Cells

2021 ◽  
Vol 22 (21) ◽  
pp. 11460
Author(s):  
Robbe Naert ◽  
Alejandro López-Requena ◽  
Karel Talavera
Keyword(s):  
T Cells ◽  
Mast Cells ◽  
Immune Cells ◽  
Tissue Injury ◽  
Nociceptive Neurons ◽  
Future Studies ◽  
Essential Step ◽  
Defensive Responses ◽  
Inflammatory Conditions ◽  
Inflammatory Bowel

The non-selective cation channel TRPA1 is best known as a broadly-tuned sensor expressed in nociceptive neurons, where it plays key functions in chemo-, thermo-, and mechano-sensing. However, in this review we illustrate how this channel is expressed also in cells of the immune system. TRPA1 has been detected, mainly with biochemical techniques, in eosinophils, mast cells, macrophages, dendritic cells, T cells, and B cells, but not in neutrophils. Functional measurements, in contrast, remain very scarce. No studies have been reported in basophils and NK cells. TRPA1 in immune cells has been linked to arthritis (neutrophils), anaphylaxis and atopic dermatitis (mast cells), atherosclerosis, renal injury, cardiac hypertrophy and inflammatory bowel disease (macrophages), and colitis (T cells). The contribution of TRPA1 to immunity is dual: as detector of cell stress, tissue injury, and exogenous noxious stimuli it leads to defensive responses, but in conditions of aberrant regulation it contributes to the exacerbation of inflammatory conditions. Future studies should aim at characterizing the functional properties of TRPA1 in immune cells, an essential step in understanding its roles in inflammation and its potential as therapeutic target.

Effects of extracts and compounds from Tricholoma populinum Lange on degranulation and IL-2/IL-8 secretion of immune cells

2017 ◽  
Vol 72 (7-8) ◽  
pp. 277-283 ◽  
Author(s):  
Simon Merdivan ◽  
Kristina Jenett-Siems ◽  
Karsten Siems ◽  
Timo H.J. Niedermeyer ◽  
Nadin Schultze ◽  
...  
Keyword(s):  
T Cells ◽  
Mast Cells ◽  
Immune Cells ◽  
Active Principle ◽  
Fruiting Bodies ◽  
Jurkat T Cells ◽  
Future Studies ◽  
Ergosterol Peroxide ◽  
The Family ◽  
Allergy Treatment

Abstract:Tricholoma populinumLange is an edible basidiomycete from the family Tricholomataceae. Extracts, fractions, and different metabolites isolated from the fruiting bodies of this mushroom were tested for degranulation-inhibiting activities on RBL-2H3 cells (rat basophils). Dichloromethane extracts decreased degranulation significantly, as did a fraction after column chromatography. In addition, the extract decreased the IL-2 release from Jurkat T cells and the release of IL-8 from HMC-1 human mast cells. The results show the significant effects of extracts ofT. populinumon cells of the innate (basophils and mast cells) and adaptive (T cells) immune system and indicate the influence of the mushroom on different immunological processes. As one fraction showed activity, it seems to be possible that it includes an active principle. The compounds responsible for this effect, however, could not be identified as the contents oleic acid (1), ergosterol peroxide (2), and 9,11-dehydroergosterol peroxide (3) showed no effects. Nevertheless, the mushroom could be used for supporting allergy treatment in future studies.

scholarly journals The immune response of T cells and therapeutic targets related to regulating the levels of T helper cells after ischaemic stroke

2021 ◽  
Vol 18 (1) ◽  
Author(s):  
Tian-Yu Lei ◽  
Ying-Ze Ye ◽  
Xi-Qun Zhu ◽  
Daniel Smerin ◽  
Li-Juan Gu ◽  
...  
Keyword(s):  
Immune Response ◽  
T Cells ◽  
Immune System ◽  
Immune Responses ◽  
Ischaemic Stroke ◽  
Immune Cells ◽  
Tissue Injury ◽  
Recovery Period ◽  
Vital Functions ◽  
Anti Inflammatory

AbstractThrough considerable effort in research and clinical studies, the immune system has been identified as a participant in the onset and progression of brain injury after ischaemic stroke. Due to the involvement of all types of immune cells, the roles of the immune system in stroke pathology and associated effects are complicated. Past research concentrated on the functions of monocytes and neutrophils in the pathogenesis of ischaemic stroke and tried to demonstrate the mechanisms of tissue injury and protection involving these immune cells. Within the past several years, an increasing number of studies have elucidated the vital functions of T cells in the innate and adaptive immune responses in both the acute and chronic phases of ischaemic stroke. Recently, the phenotypes of T cells with proinflammatory or anti-inflammatory function have been demonstrated in detail. T cells with distinctive phenotypes can also influence cerebral inflammation through various pathways, such as regulating the immune response, interacting with brain-resident immune cells and modulating neurogenesis and angiogenesis during different phases following stroke. In view of the limited treatment options available following stroke other than tissue plasminogen activator therapy, understanding the function of immune responses, especially T cell responses, in the post-stroke recovery period can provide a new therapeutic direction. Here, we discuss the different functions and temporal evolution of T cells with different phenotypes during the acute and chronic phases of ischaemic stroke. We suggest that modulating the balance between the proinflammatory and anti-inflammatory functions of T cells with distinct phenotypes may become a potential therapeutic approach that reduces the mortality and improves the functional outcomes and prognosis of patients suffering from ischaemic stroke.

scholarly journals Store-Operated Calcium Entry Controls Innate and Adaptive Immune Cell Function in Inflammatory Bowel Disease

2021 ◽  
Author(s):  
Marilena Letizia ◽  
Ulrike Kaufmann ◽  
Yin-Hu Wang ◽  
Lorenz Gerbeth ◽  
Annegret Sand ◽  
...  
Keyword(s):  
Inflammatory Bowel Disease ◽  
T Cells ◽  
T Cell ◽  
Immune Cells ◽  
Bowel Disease ◽  
Clinical Course ◽  
Lymphoid Cells ◽  
Inflammatory Bowel ◽  
The Impact ◽  
Pharmacologic Inhibition

AbstractObjectiveInflammatory bowel disease (IBD) is characterized by dysregulated intestinal immune responses and constitutes a major clinical challenge in need of new treatment modalities to improve patient care. Store-operated Ca2+ entry (SOCE) is the predominant Ca2+ influx pathway in T cells and other immune cells, regulating many of their functional properties. It is currently unknown whether the pharmacologic blockade of SOCE represents a suitable drug-target for IBD treatment.DesignUsing mass and flow cytometry the effects of SOCE inhibition on lamina propria (LP) immune cells of patients with ulcerative colitis (UC) and Crohn’s disease (CD) were investigated. Primary organoid cultures served to study the impact of SOCE inhibition on the function, differentiation and survival of intestinal epithelial cells (IEC). T cell transfer models of colitis were applied to examine how the genetic or pharmacologic ablation of SOCE affects the clinical course of IBD in mice.ResultsWe observed that the LP of IBD patients is characterized by an enrichment of innate lymphoid cells (ILC), CD4+ and CD8+ effector- as well as T regulatory cells producing IL-17 and TNFα. The pharmacologic inhibition of SOCE attenuated the production of pathogenic cytokines including IL-2, IL-4, IL-6, IL-17, TNFα and IFNγ by human colonic T cells and ILC, reduced the production of IL-6 by B cells and the production of IFNγ by myeloid cells, without affecting the viability, differentiation and function of primary IEC. T cell-specific genetic deletion of the SOCE signaling components Orai1, Stim1 or Stim2 revealed that the magnitude of SOCE correlates with the function of T cells and intestinal inflammation in mice. Moreover, the pharmacologic inhibition of SOCE alleviated the clinical course of colitic mice.ConclusionOur data suggest that SOCE inhibition may serve as a new pharmacologic strategy for treating IBD.

scholarly journals The Construction and Exploration of the CeRNA Network and Patterns of Tumor-infiltrating Immune Cells in Kidney Renal Clear Cell Carcinoma

2021 ◽  
Author(s):  
Weiwei Jia ◽  
Pengjia Li ◽  
Mingxia Ma ◽  
Xiaochen Niu ◽  
Lina Bai ◽  
...  
Keyword(s):  
T Cells ◽  
Regression Analysis ◽  
Mast Cells ◽  
Immune Cells ◽  
Prognostic Model ◽  
Cox Regression ◽  
Cox Regression Analysis ◽  
Cerna Network ◽  
Follicular Helper ◽  
Lncrna Malat1

Abstract KIRC is the malignant tumor with the highest incidence and poor prognosis in renal cell carcinoma. We want to explore the possible mechanisms of KIRC and effective prognostic-related biomarkers. The sequencing information of 3 types of RNA (mRNA, lncRNA and miRNA) in 539 cases of KIRC tissues and 72 cases of normal tissues is obtained from the TCGA database. Methods such as univariate Cox regression analysis, lasso regression screening, and multivariate Cox regression analysis were used to construct a prognostic model based on the CeRNA network. There are 3074 mRNAs, 359 lncRNAs and 132 miRNAs differentially expressed that have been identified through differential analysis. A complete mRNA-miRNA-lncRNA (SIX1-hsa-miR-200b-3p-MALAT1) network was obtained based on the CeRNA network. The CIBERSORT algorithm was used to analyze the degree of infiltration of 22 kinds of immune cells from each sample of KIRC. Construction of a prognostic model based on tumor-infiltrating immune cells, 2 immune cells (Mast cells resting, T cells follicular helper) were identified by constructing a prognostic model. There was a negative correlation between lncRNA MALAT1 and Mast cells resting (R= -0.27, P < 0.001); while there was a positive correlation between lncRNA MALAT1 and T cells follicular helper (R = 0.23, P < 0.001).

Mast Cells Reduce Gvhd Severity In Allogeneic Transplantation by Reducing the Proliferation of Conventional T Cells

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 243-243
Author(s):  
Dennis B Leveson-Gower ◽  
Emanuela I Sega ◽  
Janet Kalesnikoff ◽  
Mareike Florek ◽  
Stephen J Galli ◽  
...  
Keyword(s):  
Bone Marrow ◽  
T Cells ◽  
T Cell ◽  
Mast Cells ◽  
Bone Marrow Cells ◽  
Conflicts Of Interest ◽  
Tissue Injury ◽  
Allogeneic Transplantation ◽  
Treg Cells ◽  
Effector Cells

Abstract Abstract 243 Mast cells are important effector cells in many innate and adaptive immune responses, and can influence the function of several immune cells including granulocytes, monocytes/macrophages, dendritic cells, T cells, B cells, NK cells, and NKT cells. In contrast to their well-know pro-inflammatory roles, in certain models, mast cells have been shown to decrease inflammation and tissue injury. We explored the biological activity of mast cells in a well-established model of mouse graft-versus-host disease (GVHD) by comparing C57BL/6-KitW-sh/W-sh mice (which lack mast cells) to wild-type (WT) C57BL/6 (H-2b) recipients in a major-MHC mismatched model of allogeneic transplantation. After myeloablative irradiation, recipients received 5×106 T-cell depleted bone marrow cells from FVB/N donors (H-2q) on day 0 followed by transfer of 2×106 FVB/N CD4 and CD8 conventional T cells (Tcon) at a 2:1 ratio on day 4. A dramatic decrease in survival was observed in the animals lacking mast cells where 100% of KitW-sh/W-sh recipients died by day 15 following transplantation while over 50% of WT recipients were alive at day 60 (p < 0.0001). The exacerbated GVHD in KitW-sh/W-sh mice correlated with an increase in Tcon proliferation as indicated by bioluminescence imaging (BLI), particularly in lymph node, liver, and gastrointestinal tract tissue sites (p < 0.001). The percentage of Foxp3 positive Treg cells was similar before and after transplantation in KitW-sh/W-sh and WT recipients, and CD4+CD25hi Treg from KitW-sh/W-sh mice were capable of suppressing T cell proliferation in a mixed leukocyte reaction. When KitW-sh/W-sh mice were given 5×106 bone marrow-derived cultured mast cells (BMCMCs) i.p., mast cell re-population of the gut and peritoneal cavity was indicated by both BLI and traditional staining methods. Preliminary experiments with KitW-sh/W-sh recipients engrafted with BMCMCs i.p. 6 weeks before allogenic transplantation demonstrated improved survival in the above GVHD model, but not if the BMCMCs were derived from IL-10-/- C57BL/6 mice. Together, these results support the hypothesis that mast cells can decrease Tcon proliferation and reduce GVHD severity by a mechanism that involves production of IL-10 by mast cells but which is independent of CD4+CD25+ Treg. Disclosures: No relevant conflicts of interest to declare.

scholarly journals ATP as a Pathophysiologic Mediator of Bacteria-Host Crosstalk in the Gastrointestinal Tract

2018 ◽  
Vol 19 (8) ◽  
pp. 2371 ◽  
Author(s):  
Akie Inami ◽  
Hiroshi Kiyono ◽  
Yosuke Kurashima
Keyword(s):  
T Cells ◽  
Gastrointestinal Tract ◽  
Mast Cells ◽  
Immune Cells ◽  
Purinergic Receptors ◽  
Inflammatory Responses ◽  
Tissue Homeostasis ◽  
Commensal Bacteria ◽  
Host Cells ◽  
Extracellular Nucleotides

Extracellular nucleotides, such as adenosine triphosphate (ATP), are released from host cells including nerve termini, immune cells, injured or dead cells, and the commensal bacteria that reside in the gut lumen. Extracellular ATP interacts with the host through purinergic receptors, and promotes intercellular and bacteria-host communication to maintain the tissue homeostasis. However, the release of massive concentrations of ATP into extracellular compartments initiates acute and chronic inflammatory responses through the activation of immunocompetent cells (e.g., T cells, macrophages, and mast cells). In this review, we focus on the functions of ATP as a pathophysiologic mediator that is required for the induction and resolution of inflammation and inter-species communication.

scholarly journals Combining Bioinformatics Techniques to Study the Key Immune-Related Genes in Abdominal Aortic Aneurysm

2020 ◽  
Vol 11 ◽  
Author(s):  
Han Nie ◽  
Jiacong Qiu ◽  
Si Wen ◽  
Weimin Zhou
Keyword(s):  
Immune Response ◽  
T Cells ◽  
Abdominal Aortic Aneurysm ◽  
Mast Cells ◽  
Aortic Aneurysm ◽  
Immune Cells ◽  
Functional Enrichment ◽  
Differentially Expressed ◽  
Abdominal Aortic ◽  
Significant Difference

Approximately 13,000 people die of an abdominal aortic aneurysm (AAA) every year. This study aimed to identify the immune response-related genes that play important roles in AAA using bioinformatics approaches. We downloaded the GSE57691 and GSE98278 datasets related to AAA from the Gene Expression Omnibus database, which included 80 AAA and 10 normal vascular samples. CIBERSORT was used to analyze the samples and detect the infiltration of 22 types of immune cells and their differences and correlations. The principal component analysis showed significant differences in the infiltration of immune cells between normal vascular and AAA samples. High proportions of CD4+ T cells, activated mast cells, resting natural killer cells, and 12 other types of immune cells were found in normal vascular tissues, whereas high proportions of macrophages, CD8+ T cells, resting mast cells, and six other types of immune cells were found in AAA tissues. In the selected samples, we identified 39 upregulated (involved in growth factor activity, hormone receptor binding, and cytokine receptor activity) and 133 downregulated genes (involved in T cell activation, cell chemotaxis, and regulation of immune response mediators). The key differentially expressed immune response-related genes were screened using the STRING database and Cytoscape software. Two downregulated genes, PI3 and MAP2K1, and three upregulated genes, SSTR1, GPER1, and CCR10, were identified by constructing a protein–protein interaction network. Functional enrichment of the differentially expressed genes was analyzed, and the expression of the five key genes in AAA samples was verified using quantitative polymerase chain reaction, which revealed that MAP2K1 was downregulated in AAA, whereas SSTR1, GEPR1, and CCR10 were upregulated; there was no significant difference in PI3 expression. Our study shows that normal vascular and AAA samples can be distinguished via the infiltration of immune cells. Five genes, PI3, MAP2K1, SSTR1, GPER1, and CCR10, may play important roles in the development, diagnosis, and treatment of AAA.

scholarly journals P111 Elucidation of inflammatory infiltration of myenteric plexus in IBD

2020 ◽  
Vol 14 (Supplement_1) ◽  
pp. S191-S191
Author(s):  
J J Wiese ◽  
A Fascì ◽  
A A Kühl ◽  
B Siegmund ◽  
M S Prüß ◽  
...  
Keyword(s):  
Inflammatory Bowel Disease ◽  
T Cells ◽  
B Cells ◽  
Cd8 T Cells ◽  
Immune Cells ◽  
Bowel Disease ◽  
Myenteric Plexus ◽  
Pain Catastrophizing ◽  
Visual Analogue Scale Pain ◽  
Inflammatory Bowel

Abstract Background Since IBD is frequently associated with chronic abdominal pain and visceral hypersensitivity, affections to the sensory nerves within the ENS appear to be pivotal. In both inflammatory bowel diseases, i.e. the transmural inflammation of Crohn’s disease (CD) and the inflammation restricted to the colonic mucosa in ulcerative colitis (UC) infiltrations of the plexus by immune cells occur. However, the type of immune cells involved is so far unknown. Therefore, we characterised the immune cell infiltrations of myenteric plexus (MP) in CD and UC compared with controls. Methods We identified 12 IBD patients (four CD and eight UC) and four controls that had received surgery (ileocecal resections or colectomy). The severity of the disease was assessed by Mayo score, HBI score and questionnaires (Visual Analogue Scale, Pain Catastrophizing Scale, Inflammatory bowel disease quality of life and Irritable Bowel Symptom Severity Scale). Formalin-fixed, paraffin-embedded tissue was stained by classical immunohistochemistry. To identify myenteric plexus tissue was stained for CGRP and PGP9.5. Immunostainings for immune cells (T cells: CD3, CD4, CD8, Foxp3; B cells: CD20; monocytes/macrophages: CD68 and CD163) were analysed by quantifying within the plexus and within a defined area of 100 µm around the plexus. Results The mean size of myenteric ganglia in controls was found to be 0.100 ± 0.004 mm² and was significantly decreased in CD (0.055 ± 0.002 mm²) and UC (0.079 ± 0.004 mm²). The population of CD4+ T-cells, macrophages and monocytes within ganglia of the MP were unchanged in CD, UC. However, infiltrates within and around MP contained significantly more CD3+ T cells in CD (121 ± 63 intraganglionic cells/mm² and 1858 ± 1133 periganglionic cells/mm²) and UC (133 ± 80 intraganglionic cells/mm² and 1198 ± 693 periganglionic cells/mm²) compared with controls (28 ± 38 intraganglionic cells/mm² and 342 ± 93 periganglionic cells/mm²). This appeared to be secondary to a significant increase of periganglionic CD8+ T cells in UC (342 ± 293 cells/mm² compared with 164 ± 140 cells/mm² in controls) (see Figure 1) and secondary to a significant increase of periganglionic Foxp3+ T cells in CD (528 ± 193 cells/mm² compared with 0 ± 0 cells/mm² in controls). Moreover, CD20+ B cells were significantly increased in CD (528 ± 193 periganglionic cells/mm² compared with 0 ± 0 periganglionic cells/mm² in controls). Conclusion The intra- and periganglionic infiltrate of MP in inflammatory bowel disease contains CD3+CD8+ T cells in UC and CD3+Foxp3+ regulatory T cells as well as B cells in CD.

scholarly journals High Mast Cell Density Predicts a Favorable Prognosis in Patients with Pancreatic Neuroendocrine Neoplasms

2021 ◽  
Author(s):  
Shengwei Mo ◽  
Liju Zong ◽  
Xianlong Chen ◽  
Xiaoyan Chang ◽  
Zhaohui Lu ◽  
...  
Keyword(s):  
T Cells ◽  
Mast Cell ◽  
Mast Cells ◽  
Cell Density ◽  
Immune Cells ◽  
Clinicopathological Parameters ◽  
Neuroendocrine Neoplasms ◽  
Pancreatic Neuroendocrine Neoplasms ◽  
Entire Cohort ◽  
Mast Cell Density

Introduction: Mast cells are involved in allergic diseases, immune regulation, and tumor microenvironment modulation, with both pro- and anti-tumorigenic functions, and could serve as a prognostic factor in various cancers. However, their potential role in pancreatic neuroendocrine neoplasms (PanNENs) is largely unknown. Here, our aim was to investigate the presence of mast cells in PanNENs and evaluate their association with clinicopathological parameters and other common tumor-infiltrating immune cells. Methods: Tissue microarrays containing PanNEN samples from 187 patients were constructed and stained immunohistochemically for CD117, CD15, CD68, CD3, CD4, and CD8. Immune cells were counted from four high-power fields (HPFs; 400×) at maximal concentrations, and the mean counts were calculated per HPF. The cut-off values were set by X-tile. Results: The median (interquartile range) counts of CD117+ mast cells, CD15+ neutrophils, CD68+ macrophages, CD3+ T cells, and CD4+ T cells were 3.5 (2.0–6.0), 3.0 (1.3–6), 3.8 (2.5–5.8), 13 (8.0–24.0), 2.0 (1.0–4.0)/HPF, respectively. CD8+ T cells were not detected. The cut-off values for these immune cells were 1.5/HPF, 6/HPF, 4.8/HPF, 32.5/HPF, and 2/HPF, respectively. Low mast cell density was correlated with higher grades, non-insulinoma, and advanced stages. Moreover, high mast cell infiltration was associated with elevated CD4+ T cell and CD15+ neutrophil counts. Multivariate analysis revealed that high mast cell density was an independent predictor of prolonged progression-free survival in the entire cohort, in pancreatic neuroendocrine tumors, and in intermediate-grade, non-insulinoma, and advanced stage subgroups. Conclusions: These findings suggest a protective role of mast cells in PanNENs.

scholarly journals γδ T cells do not contribute to peripheral inflammatory pain

2018 ◽  
Author(s):  
Jelena Petrović ◽  
Jaqueline Raymondi Silva ◽  
Julia P. Segal ◽  
Abigail S. Marshall ◽  
Cortney M. Haird ◽  
...  
Keyword(s):  
T Cells ◽  
Immune Cells ◽  
Inflammatory Pain ◽  
Tissue Injury ◽  
Γδ T Cells ◽  
Intraplantar Injection ◽  
Baseline Sensitivity ◽  
Peripheral Tissues ◽  
Transgenic Mouse Line ◽  
Thermal Hypersensitivity

AbstractCirculating immune cells, which are recruited to the site of injury/disease, secrete various inflammatory mediators that are critical to nociception and pain. The role of tissue-resident immune cells, however, remains poorly characterized. One of the first cells to be activated in peripheral tissues following injury are γδ T cells, which serve important roles in infection and disease. Using a transgenic mouse line lacking these cells, we sought to identify their contribution to inflammatory pain. Three distinct models of inflammatory pain were used: intraplantar injection of formalin and incisional wound (as models of acute inflammatory pain) and intraplantar injection of complete Freund’s adjuvant (as a model of chronic inflammatory pain). Our results show that absence of these cells does not alter baseline sensitivity, nor does it result in changes to mechanical or thermal hypersensitivity after tissue injury. These results were consistent in both male and female mice, suggesting that there are no sex differences in these outcomes. This comprehensive characterization suggests that γδ T cells do not contribute to basal sensitivity or the development and maintenance of inflammatory pain.

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