scholarly journals Comprehensive Transcriptomic Comparison between Porcine CD8− and CD8+ Gamma Delta T Cells Revealed Distinct Immune Phenotype

Animals ◽  
2021 ◽  
Vol 11 (8) ◽  
pp. 2165
Author(s):  
Sangwook Kim ◽  
Byeonghwi Lim ◽  
Sameer-ul-Salam Mattoo ◽  
Eun-Young Oh ◽  
Chang-Gi Jeong ◽  
...  
Keyword(s):  
T Cells ◽  
Signaling Pathway ◽  
Γδ T Cells ◽  
Cell Receptor ◽  
Cytokine Receptor ◽  
Receptor Interaction ◽  
Sequencing Analysis ◽  
Gamma Delta ◽  
Tcr Signaling ◽  
The Common

We aimed to comprehensively understand the functional mechanisms of immunity, especially of the CD8+/− subsets of gamma delta (γδ) T cells, using an RNA-sequencing analysis. Herein, γδ T cells were obtained from bronchial lymph node tissues of 38-day-old (after weaning 10-day: D10) and 56-day-old (after weaning 28-day: D28) weaned pigs and sorted into CD8+ and CD8− groups. Differentially expressed genes (DEGs) were identified based on the CD8 groups at D10 and D28 time points. We confirmed 1699 DEGs between D10 CD8+ versus D10 CD8− groups and 1784 DEGs between D28 CD8+ versus D28 CD8− groups; 646 upregulated and 561 downregulated DEGs were common. The common upregulated DEGs were enriched in the cytokine–cytokine receptor interaction and T cell receptor (TCR) signaling pathway, and the common downregulated DEGs were enriched in the B cell receptor signaling pathway. Further, chemokine-related genes, interferon gamma, and CD40 ligand were involved in the cytokine–cytokine receptor interaction and TCR signaling pathway, which are associated with inter-regulation in immunity. We expect our results to form the basic data required for understanding the mechanisms of γδ T cells in pigs; however, further studies are required in order to reveal the dynamic changes in γδ T cells under pathogenic infections, such as those by viruses.

scholarly journals Transcriptome Signature of Vγ9Vδ2 T Cells Treated With Phosphoantigens and Notch Inhibitor Reveals Interplay Between TCR and Notch Signaling Pathways

2021 ◽  
Vol 12 ◽  
Author(s):  
Ayush Madhok ◽  
Sajad Ahmad Bhat ◽  
Chinna Susan Philip ◽  
Shalini Kashipathi Sureshbabu ◽  
Shubhada Chiplunkar ◽  
...  
Keyword(s):  
T Cells ◽  
Notch Signaling ◽  
Interleukin 2 ◽  
Γδ T Cells ◽  
Cell Receptor ◽  
Gamma Delta ◽  
Tcr Signaling ◽  
Transcriptional Changes ◽  
Vγ9vδ2 T Cells ◽  
Cytokine Stimulation

Gamma delta (γδ) T cells, especially the Vγ9Vδ2 subtype, have been implicated in cancer therapy and thus have earned the spotlight in the past decade. Although one of the most important properties of γδ T cells is their activation by phosphoantigens, which are intermediates of the Mevalonate and Rohmer pathway of isoprenoid biosynthesis, such as IPP and HDMAPP, respectively, the global effects of such treatments on Vγ9Vδ2 T cells remain elusive. Here, we used the high-throughput transcriptomics approach to elucidate the transcriptional changes in human Vγ9Vδ2 T cells upon HDMAPP, IPP, and anti-CD3 treatments in combination with interleukin 2 (IL2) cytokine stimulation. These activation treatments exhibited a dramatic surge in transcription with distinctly enriched pathways. We further assessed the transcriptional dynamics upon inhibition of Notch signaling coupled with activation treatments. We observed that the metabolic processes are most affected upon Notch inhibition via GSI-X. The key effector genes involved in gamma–delta cytotoxic function were downregulated upon Notch blockade even in combination with activation treatment, suggesting a transcriptional crosstalk between T-cell receptor (TCR) signaling and Notch signaling in Vγ9Vδ2 T cells. Collectively, we demonstrate the effect of the activation of TCR signaling by phosphoantigens or anti-CD3 on the transcriptional status of Vγ9Vδ2 T cells along with IL2 stimulation. We further show that the blockade of Notch signaling antagonistically affects this activation.

scholarly journals Leukocyte-associated immunoglobulin-like receptor 1 inhibits T-cell signaling by decreasing protein phosphorylation in the T-cell signaling pathway

2020 ◽  
Vol 295 (8) ◽  
pp. 2239-2247 ◽  
Author(s):  
Jeoung-Eun Park ◽  
David D. Brand ◽  
Edward F. Rosloniec ◽  
Ae-Kyung Yi ◽  
John M. Stuart ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Tyrosine Kinase ◽  
Cell Signaling ◽  
Signaling Pathway ◽  
T Cell Receptor ◽  
Cell Receptor ◽  
T Cell Signaling ◽  
Tcr Signaling ◽  
Cell Signaling Pathway

Multiple observations implicate T-cell dysregulation as a central event in the pathogenesis of rheumatoid arthritis. Here, we investigated mechanisms for suppressing T-cell activation via the inhibitory receptor leukocyte-associated immunoglobulin-like receptor 1 (LAIR-1). To determine how LAIR-1 affects T-cell receptor (TCR) signaling, we compared 1) T cells from LAIR-1–sufficient and –deficient mice, 2) Jurkat cells expressing either LAIR-1 mutants or C-terminal Src kinase (CSK) mutants, and 3) T cells from mice that contain a CSK transgene susceptible to chemical inhibition. Our results indicated that LAIR-1 engagement by collagen or by complement C1q (C1Q, which contains a collagen-like domain) inhibits TCR signaling by decreasing the phosphorylation of key components in the canonical T-cell signaling pathway, including LCK proto-oncogene SRC family tyrosine kinase (LCK), LYN proto-oncogene SRC family tyrosine kinase (LYN), ζ chain of T-cell receptor–associated protein kinase 70 (ZAP-70), and three mitogen-activated protein kinases (extracellular signal–regulated kinase, c-Jun N-terminal kinase 1/2, and p38). The intracellular region of LAIR-1 contains two immunoreceptor tyrosine-based inhibition motifs that are both phosphorylated by LAIR-1 activation, and immunoprecipitation experiments revealed that Tyr-251 in LAIR-1 binds CSK. Using CRISPR/Cas9-mediated genome editing, we demonstrate that CSK is essential for the LAIR-1–induced inhibition of the human TCR signal transduction. T cells from mice that expressed a PP1 analog–sensitive form of CSK (CskAS) corroborated these findings, and we also found that Tyr-251 is critical for LAIR-1's inhibitory function. We propose that LAIR-1 activation may be a strategy for controlling inflammation and may offer a potential therapeutic approach for managing autoimmune diseases.

Lactobacillus rhamnosus GG alleviates β-conglycinin-induced allergy by regulating the T cell receptor signaling pathway

2020 ◽  
Vol 11 (12) ◽  
pp. 10554-10567 ◽  
Author(s):  
Xiaoxu Chen ◽  
Xiuli Zhao ◽  
Yaozhong Hu ◽  
Bowei Zhang ◽  
Yan Zhang ◽  
...  
Keyword(s):  
T Cells ◽  
Signaling Pathway ◽  
T Cell Receptor ◽  
Lactobacillus Rhamnosus ◽  
Cell Receptor ◽  
Tcr Signaling ◽  
Lactobacillus Rhamnosus Gg ◽  
T Cell Receptor Signaling ◽  
Receptor Signaling Pathway ◽  
Cell Receptor Signaling

LGG alleviates the β-CG induced allergic response by regulating the differentiation of T cells, maintains the balance of Th1/Th2 and Th17/Treg via the TCR signaling pathway.

scholarly journals In the Absence of a TCR Signal IL-2/IL-12/18-Stimulated γδ T Cells Demonstrate Potent Anti-Tumoral Function Through Direct Killing and Senescence Induction in Cancer Cells

Cancers ◽  
2020 ◽  
Vol 12 (1) ◽  
pp. 130 ◽  
Author(s):  
Karin Schilbach ◽  
Christian Welker ◽  
Naomi Krickeberg ◽  
Carlotta Kaißer ◽  
Sabine Schleicher ◽  
...  
Keyword(s):  
T Cells ◽  
Cancer Cells ◽  
Adoptive Cell Therapy ◽  
Γδ T Cells ◽  
Cell Receptor ◽  
Tcr Signaling ◽  
Tumor Recognition ◽  
Ifn Γ ◽  
The Impact ◽  
Anti Tumor Activity

Abundant IFN-γ secretion, potent cytotoxicity, and major histocompatibility complex-independent targeting of a large spectrum of tumors make γδ T cells attractive candidates for cancer immunotherapy. Upon tumor recognition through the T-cell receptor (TCR), NK-receptors, or NKG2D, γδ T cells generate the pro-inflammatory cytokines TNF-α and IFN-γ, or granzymes and perforin that mediate cellular apoptosis. Despite these favorable potentials, most clinical trials testing the adoptive transfer of pharmacologically TCR-targeted and expanded γδ T cells resulted in a limited response. Recently, the TCR-independent activation of γδ T cells was identified. However, the modulation of γδ T cell’s effector functions solely by cytokines remains to be elucidated. In the present study, we systematically analyzed the impact of IL-2, IL-12, and IL-18 in parallel with TCR stimulation on proliferation, cytokine production, and anti-tumor activity of γδ T cells. Our results demonstrate that IL-12 and IL-18, when combined, constitute the most potent stimulus to enhance anti-tumor activity and induce proliferation and IFN-γ production by γδ T cells in the absence of TCR signaling. Intriguingly, stimulation with IL-12 and IL-18 without TCR stimulus induces a comparable degree of anti-tumor activity in γδ T cells to TCR crosslinking by killing tumor cells and driving cancer cells into senescence. These findings approve the use of IL-12/IL-18-stimulated γδ T cells for adoptive cell therapy to boost anti-tumor activity by γδ T cells.

Abstract 025: Lacking of Gamma Delta T Cells Exaggerate Cardiac Dysfunction in Angiotensin II-induced Hypertension in Balb/cByJ Mice

Hypertension ◽  
2017 ◽  
Vol 70 (suppl_1) ◽  
Author(s):  
Tang-Dong Liao ◽  
Jiang Xu ◽  
Oscar A Carretero
Keyword(s):  
T Cells ◽  
Cardiac Function ◽  
Γδ T Cells ◽  
Adaptive Immune System ◽  
Cell Receptor ◽  
Organ Damage ◽  
Ang Ii ◽  
Gamma Delta ◽  
Induced Hypertension ◽  
Eccentric Hypertrophy

Gamma Delta T lymphocytes are important innate immune component which express γδ T cell receptor (TCR). These cells are capable of spontaneous secretion of IL-17 and IFN gamma proinflammatory cytokines. Recently, new evidence suggests that the innate and adaptive immune system is involved in the hypertension and end-organ damage. We tested the hypothesis whether deficiency in γδ TCR has a beneficial effect on cardiac function in Angiotension II (Ang II)-induced hypertension. Male Balb/cByj wild-type (WT) and Tcrγδ knockout (Tcrγδ-/-) mice were infused with vehicle or Ang II at dosage of 400ng/kg/min for 4 weeks. Our results showed Systolic blood pressure (SBP) was increased significantly after 1 week of Ang II infusion, and the increase was sustained 4 weeks in WT mice, however in Tcrγδ-/- mice, SBP dropped significantly at 4 weeks compared to WT (table1). Echocardiography data showed that ejection fraction (EF) and shortening fraction (SF) were decreased significantly after Ang II infusion; these effects were exacerbated in Tcrγδ-/- mice given Ang II. Also both mass and chamber dimension increased greater in Tcrγδ-/- mice given Ang II compared to WT (table1). The results indicated Tcrγδ-/- mice given Ang II develop eccentric hypertrophy. We conclude that lacking of γδ T cells has a detrimental effect on cardiac function in Ang II-induced hypertension in Balb/cByJ mice. table1:

scholarly journals T cell receptor signaling pathway and cytokine-cytokine receptor interaction affect the rehabilitation process after respiratory syncytial virus infection

PeerJ ◽  
2019 ◽  
Vol 7 ◽  
pp. e7089 ◽  
Author(s):  
Zuanhao Qian ◽  
Zhenglei Zhang ◽  
Yingying Wang
Keyword(s):  
T Cell ◽  
Signaling Pathway ◽  
T Cell Receptor ◽  
Cell Receptor ◽  
Cytokine Receptor ◽  
Receptor Interaction ◽  
T Cell Receptor Signaling ◽  
Rsv Infection ◽  
Receptor Signaling Pathway ◽  
Cell Receptor Signaling

Background Respiratory syncytial virus (RSV) is the main cause of respiratory tract infection, which seriously threatens the health and life of children. This study is conducted to reveal the rehabilitation mechanisms of RSV infection. Methods E-MTAB-5195 dataset was downloaded from EBI ArrayExpress database, including 39 acute phase samples in the acute phase of infection and 21 samples in the recovery period. Using the limma package, differentially expressed RNAs (DE-RNAs) were analyzed. The significant modules were identified using WGCNA package, and the mRNAs in them were conducted with enrichment analysis using DAVID tool. Afterwards, co-expression network for the RNAs involved in the significant modules was built by Cytoscape software. Additionally, RSV-correlated pathways were searched from Comparative Toxicogenomics Database, and then the pathway network was constructed. Results There were 2,489 DE-RNAs between the two groups, including 2,386 DE-mRNAs and 103 DE-lncRNAs. The RNAs in the black, salmon, blue, tan and turquoise modules correlated with stage were taken as RNA set1. Meanwhile, the RNAs in brown, blue, magenta and pink modules related to disease severity were defined as RNA set2. In the pathway networks, CD40LG and RASGRP1 co-expressed with LINC00891/LINC00526/LINC01215 were involved in the T cell receptor signaling pathway, and IL1B, IL1R2, IL18, and IL18R1 co-expressed with BAIAP2-AS1/CRNDE/LINC01503/SMIM25 were implicated in cytokine-cytokine receptor interaction. Conclusion LINC00891/LINC00526/LINC01215 co-expressed with CD40LG and RASGRP1 might affect the rehabilitation process of RSV infection through the T cell receptor signaling pathway. Besides, BAIAP2-AS1/CRNDE/LINC01503/SMIM25 co-expressed with IL1 and IL18 families might function in the clearance process after RSV infection via cytokine-cytokine receptor interaction.

scholarly journals The Common Cytokine Receptor γ Chain Plays an Essential Role in Regulating Lymphoid Homeostasis

1997 ◽  
Vol 185 (2) ◽  
pp. 189-196 ◽  
Author(s):  
Hiroshi Nakajima ◽  
Elizabeth W. Shores ◽  
Masayuki Noguchi ◽  
Warren J. Leonard
Keyword(s):  
T Cells ◽  
Cd4 T Cells ◽  
Lymphocyte Proliferation ◽  
Cell Receptor ◽  
Cytokine Receptor ◽  
Proliferating Cells ◽  
Lymphoid Development ◽  
Age Dependent ◽  
The Common ◽  
Deficient Mice

In the immune system, there is a careful regulation not only of lymphoid development and proliferation, but also of the fate of activated and proliferating cells. Although the manner in which these diverse events are coordinated is incompletely understood, cytokines are known to play major roles. Whereas IL-7 is essential for lymphoid development, IL-2 and IL-4 are vital for lymphocyte proliferation. The receptors for each of these cytokines contain the common cytokine receptor γ chain (γc), and it was previously shown that γc-deficient mice exhibit severely compromised development and responsiveness to IL-2, IL-4, and IL-7. Nevertheless, these mice exhibit an age-dependent accumulation of splenic CD4+ T cells, the majority of which have a phenotype typical of memory/activated cells. When γc-deficient mice were mated to DO11.10 T cell receptor (TCR) transgenic mice, only the T cells bearing endogenous TCRs had this phenotype, suggesting that its acquisition was TCR dependent. Not only do the CD4+ T cells from γc-deficient mice exhibit an activated phenotype and greatly enhanced incorporation of bromodeoxyuridine but, consistent with the lack of γc-dependent survival signals, they also exhibit an augmented rate of apoptosis. However, because the CD4+ T cells accumulate, it is clear that the rate of proliferation exceeds the rate of cell death. Thus, surprisingly, although γc-independent signals are sufficient to mediate expansion of CD4+ T cells in these mice, γc-dependent signals are required to regulate the fate of activated CD4+ T cells, underscoring the importance of γc-dependent signals in controlling lymphoid homeostasis.

scholarly journals Targeting CAR to the Peptide-MHC Complex Reveals Distinct Signaling Compared to That of TCR in a Jurkat T Cell Model

Cancers ◽  
2021 ◽  
Vol 13 (4) ◽  
pp. 867
Author(s):  
Ling Wu ◽  
Joanna Brzostek ◽  
Shvetha Sankaran ◽  
Qianru Wei ◽  
Jiawei Yap ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cell Model ◽  
Cell Receptor ◽  
Target Cells ◽  
Tcr Signaling ◽  
Barr Virus ◽  
Car T ◽  
Epstein Barr ◽  
Lower Magnitude

Chimeric antigen receptor T cells (CAR-T) utilize T cell receptor (TCR) signaling cascades and the recognition functions of antibodies. This allows T cells, normally restricted by the major histocompatibility complex (MHC), to be redirected to target cells by their surface antigens, such as tumor associated antigens (TAAs). CAR-T technology has achieved significant successes in treatment of certain cancers, primarily liquid cancers. Nonetheless, many challenges hinder development of this therapy, such as cytokine release syndrome (CRS) and the efficacy of CAR-T treatments for solid tumors. These challenges show our inadequate understanding of this technology, particularly regarding CAR signaling, which has been less studied. To dissect CAR signaling, we designed a CAR that targets an epitope from latent membrane protein 2 A (LMP2 A) of the Epstein–Barr virus (EBV) presented on HLA*A02:01. Because of this, CAR and TCR signaling can be compared directly, allowing us to study the involvement of other signaling molecules, such as coreceptors. This comparison revealed that CAR was sufficient to bind monomeric antigens due to its high affinity but required oligomeric antigens for its activation. CAR sustained the transduced signal significantly longer, but at a lower magnitude, than did TCR. CD8 coreceptor was recruited to the CAR synapse but played a negligible role in signaling, unlike for TCR signaling. The distinct CAR signaling processes could provide explanations for clinical behavior of CAR-T therapy and suggest ways to improve the technology.

scholarly journals Identification of upregulated NF-κB inhibitor alpha and IRAK3 targeting lncRNA following intracranial aneurysm rupture-induced subarachnoid hemorrhage

BMC Neurology ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Wei Leng ◽  
Dan Fan ◽  
Zhong Ren ◽  
Qiaoying Li
Keyword(s):  
Subarachnoid Hemorrhage ◽  
Intracranial Aneurysm ◽  
Signaling Pathway ◽  
Aneurysm Rupture ◽  
Cytokine Receptor ◽  
Gene Set Enrichment Analysis ◽  
Receptor Interaction ◽  
Regulatory Pathways ◽  
Ruptured Intracranial Aneurysm ◽  
Neurotrophin Signaling

Abstract Background This study was performed to identify genes and lncRNAs involved in the pathogenesis of subarachnoid hemorrhage (SAH) from ruptured intracranial aneurysm (RIA). Methods Microarray GSE36791 was downloaded from Gene Expression Omnibus (GEO) database followed by the identification of significantly different expressed RNAs (DERs, including lncRNA and mRNA) between patients with SAH and healthy individuals. Then, the functional analyses of DEmRNAs were conducted and weighted gene co-expression network analysis (WGCNA) was also performed to extract the modules associated with SAH. Following, the lncRNA-mRNA co-expression network was constructed and the gene set enrichment analysis (GSEA) was performed to screen key RNA biomarkers involved in the pathogenesis of SAH from RIA. We also verified the results in a bigger dataset GSE7337. Results Totally, 561 DERs, including 25 DElncRNAs and 536 DEmRNAs, were identified. Functional analysis revealed that the DEmRNAs were mainly associated with immune response-associated GO-BP terms and KEGG pathways. Moreover, there were 6 modules significantly positive-correlated with SAH. The lncRNA-mRNA co-expression network contained 2 lncRNAs (LINC00265 and LINC00937) and 169 mRNAs. The GSEA analysis showed that these two lncRNAs were associated with three pathways (cytokine-cytokine receptor interaction, neurotrophin signaling pathway, and apoptosis). Additionally, IRAK3 and NFKBIA involved in the neurotrophin signaling pathway and apoptosis while IL1R2, IL18RAP and IL18R1 was associated with cytokine-cytokine receptor interaction pathway. The expression levels of these genes have the same trend in GSE36791 and GSE7337. Conclusion LINC00265 and LINC00937 may be implicated with the pathogenesis of SAH from RIA. They were involved in three important regulatory pathways. 5 mRNAs played important roles in the three pathways.

An obligate role for T-cell receptor αβ+ T cells but not T-cell receptor γδ+ T cells, B cells, or CD40/CD40L interactions in a mouse model of atopic dermatitis

2001 ◽  
Vol 107 (2) ◽  
pp. 359-366 ◽  
Author(s):  
Amy L. Woodward ◽  
Jonathan M. Spergel ◽  
Harri Alenius ◽  
Emiko Mizoguchi ◽  
Atul K. Bhan ◽  
...  
Keyword(s):  
T Cells ◽  
Atopic Dermatitis ◽  
T Cell ◽  
B Cells ◽  
Mouse Model ◽  
T Cell Receptor ◽  
Γδ T Cells ◽  
Cell Receptor ◽  
Αβ T Cells
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