scholarly journals Influence of PTPN22 Allotypes on Innate and Adaptive Immune Function in Health and Disease

2021 ◽  
Vol 12 ◽  
Author(s):  
Lucas H. Armitage ◽  
Mark A. Wallet ◽  
Clayton E. Mathews
Keyword(s):  
Cell Function ◽  
Immune Cell ◽  
Tyrosine Phosphatase ◽  
Cell Receptor ◽  
Tcr Signaling ◽  
Increased Risk ◽  
Core Function ◽  
Health And Disease

Protein tyrosine phosphatase, non-receptor type 22 (PTPN22) regulates a panoply of leukocyte signaling pathways. A single nucleotide polymorphism (SNP) in PTPN22, rs2476601, is associated with increased risk of Type 1 Diabetes (T1D) and other autoimmune diseases. Over the past decade PTPN22 has been studied intensely in T cell receptor (TCR) and B cell receptor (BCR) signaling. However, the effect of the minor allele on PTPN22 function in TCR signaling is controversial with some reports concluding it has enhanced function and blunts TCR signaling and others reporting it has reduced function and increases TCR signaling. More recently, the core function of PTPN22 as well as functional derangements imparted by the autoimmunity-associated variant allele of PTPN22 have been examined in monocytes, macrophages, dendritic cells, and neutrophils. In this review we will discuss the known functions of PTPN22 in human cells, and we will elaborate on how autoimmunity-associated variants influence these functions across the panoply of immune cells that express PTPN22. Further, we consider currently unresolved questions that require clarification on the role of PTPN22 in immune cell function.

scholarly journals Induction of T Cell Senescence by Cytokine Induced Bystander Activation

2021 ◽  
Vol 2 ◽  
Author(s):  
Attiya A. Abbas ◽  
Arne N. Akbar
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cell Function ◽  
Immune Cell ◽  
Critical Role ◽  
The Elderly ◽  
Cell Receptor ◽  
Antigen Specificity ◽  
Tcr Signaling ◽  
Bystander Activation

As people around the world continue to live longer, maintaining a good quality of life is of increasing importance. The COVID-19 pandemic revealed that the elderly are disproportionally vulnerable to infectious diseases and Immunosenescence plays a critical role in that. An ageing immune system influences the conventional activity of T cells which are at the forefront of eliminating harmful foreign antigens. With ageing, unconventional end-stage T cells, that exhibit a senescent phenotype, amass. These senescent T cells deviate from T cell receptor (TCR) signaling toward natural killer (NK) activity. The transition toward innate immune cell function from these adaptor T cells impacts antigen specificity, contributing to increased susceptibility of infection in the elderly. The mechanism by which senescent T cells arise remains largely unclear however in this review we investigate the part that bystander activation plays in driving the change in function of T cells with age. Cytokine-induced bystander activation may offer a plausible explanation for the induction of NK-like activity and senescence in T cells. Further understanding of these specific NK-like senescent T cells allows us to identify the benefits and detriments of these cells in health and disease which can be utilized or regulated, respectively. This review discusses the dynamic of senescent T cells in adopting NK-like T cells and the implications that has in an infectious disease context, predominately in the elderly.

scholarly journals Cannabinoids and the Immune System

2001 ◽  
Vol 6 (2) ◽  
pp. 95-101 ◽  
Author(s):  
Thomas W Klein ◽  
Catherine A Newton ◽  
Herman Friedman
Keyword(s):  
Cannabinoid Receptors ◽  
Cell Function ◽  
Immune Cell ◽  
Immune Deficiency Syndrome ◽  
Deficiency Syndrome ◽  
Cannabinoid System ◽  
Health And Disease ◽  
And Function ◽  
Acquired Immune Deficiency

The effect of cannabimimetic agents on the function of immune cells such as T and B lymphocytes, natural killer cells and macrophages has been extensively studied over the past several decades using human and animal paradigms involving whole animal models as well as tissue culture systems. From this work, it can be concluded that these drugs have subtle yet complex effects on immune cell function and that some of the drug activity is mediated by cannabinoid receptors expressed on the various immune cell subtypes. However, the overall role of the cannabinoid system of receptors and ligands in human health and disease is still unclear and requires extensive elucidation. Further studies will define the precise structure and function of the putative immunocannabinoid system, the potential therapeutic usefulness of these drugs in chronic diseases such as acquired immune deficiency syndrome and multiple sclerosis, the effects of these agents on tumour growth and induction of apoptosis, and the potential anti-inflammatory and proinflammatory properties of cannabimimetic compounds. It is likely that the cannabinoid system, along with other neuroimmune systems, has a subtle but significant role in the regulation of immunity and that this role can eventually be exploited in the management of human disease.

scholarly journals Molecular regulation of TLR signaling in health and disease: mechano-regulation of macrophages and TLR signaling

2020 ◽  
Vol 26 (1) ◽  
pp. 15-25 ◽  
Author(s):  
Erika J Gruber ◽  
Cynthia A Leifer
Keyword(s):  
Cell Function ◽  
Immune Cell ◽  
Tissue Mechanics ◽  
Physical Characteristics ◽  
Immune Cell Function ◽  
Tlr Signaling ◽  
Cytokines And Chemokines ◽  
Health And Disease ◽  
Sense And Respond

Immune cells encounter tissues with vastly different biochemical and physical characteristics. Much of the research emphasis has focused on the role of cytokines and chemokines in regulating immune cell function, but the role of the physical microenvironment has received considerably less attention. The tissue mechanics, or stiffness, of healthy tissues varies dramatically from soft adipose tissue and brain to stiff cartilage and bone. Tissue mechanics also change due to fibrosis and with diseases such as atherosclerosis or cancer. The process by which cells sense and respond to their physical microenvironment is called mechanotransduction. Here we review mechanotransduction in immunologically important diseases and how physical characteristics of tissues regulate immune cell function, with a specific emphasis on mechanoregulation of macrophages and TLR signaling.

scholarly journals The Role of the Adipokine Leptin in Immune Cell Function in Health and Disease

2021 ◽  
Vol 11 ◽  
Author(s):  
Kaitlin Kiernan ◽  
Nancie J. MacIver
Keyword(s):  
Adipose Tissue ◽  
Leptin Receptor ◽  
Cell Function ◽  
Immune Cell ◽  
Immune Cell Function ◽  
Tissue Mass ◽  
Inflammatory Phenotype ◽  
Health And Disease ◽  
Pleiotropic Actions

Leptin is a critical mediator of the immune response to changes in overall nutrition. Leptin is produced by adipocytes in proportion to adipose tissue mass and is therefore increased in obesity. Despite having a well-described role in regulating systemic metabolism and appetite, leptin displays pleiotropic actions, and it is now clear that leptin has a key role in influencing immune cell function. Indeed, many immune cells have been shown to respond to leptin directly via the leptin receptor, resulting in a largely pro-inflammatory phenotype. Understanding the role of adipose-tissue derived mediators in inflammation is critical to determining the pathophysiology of multiple obesity-associated diseases, such as type 2 diabetes, autoimmune disease, and infection. This review, therefore, focuses on the latest data regarding the role of leptin in modulating inflammation.

scholarly journals Longitudinal Expression of Testicular TAS1R3 from Prepuberty to Sexual Maturity in Congjiang Xiang Pigs

Animals ◽  
2021 ◽  
Vol 11 (2) ◽  
pp. 437
Author(s):  
Ting Gong ◽  
Weiyong Wang ◽  
Houqiang Xu ◽  
Yi Yang ◽  
Xiang Chen ◽  
...  
Keyword(s):  
Sexual Maturity ◽  
Cell Function ◽  
Expression Patterns ◽  
Taste Receptor ◽  
Receptor Type ◽  
Mrna Levels ◽  
Early Puberty ◽  
Specific Expression

Testicular expression of taste receptor type 1 subunit 3 (T1R3), a sweet/umami taste receptor, has been implicated in spermatogenesis and steroidogenesis in mice. We explored the role of testicular T1R3 in porcine postnatal development using the Congjiang Xiang pig, a rare Chinese miniature pig breed. Based on testicular weights, morphology, and testosterone levels, four key developmental stages were identified in the pig at postnatal days 15–180 (prepuberty: 30 day; early puberty: 60 day; late puberty: 90 day; sexual maturity: 120 day). During development, testicular T1R3 exhibited stage-dependent and cell-specific expression patterns. In particular, T1R3 levels increased significantly from prepuberty to puberty (p < 0.05), and expression remained high until sexual maturity (p < 0.05), similar to results for phospholipase Cβ2 (PLCβ2). The strong expressions of T1R3/PLCβ2 were observed at the cytoplasm of elongating/elongated spermatids and Leydig cells. In the eight-stage cycle of the seminiferous epithelium in pigs, T1R3/PLCβ2 levels were higher in the spermatogenic epithelium at stages II–VI than at the other stages, and the strong expressions were detected in elongating/elongated spermatids and residual bodies. The message RNA (mRNA) levels of taste receptor type 1 subunit 1 (T1R1) in the testis showed a similar trend to levels of T1R3. These data indicate a possible role of T1R3 in the regulation of spermatid differentiation and Leydig cell function.

scholarly journals Polymorphism in BACH2 gene is a marker of polyglandular autoimmunity

Endocrine ◽  
2021 ◽  
Author(s):  
Marta Fichna ◽  
Magdalena Żurawek ◽  
Bartosz Słomiński ◽  
Marta Sumińska ◽  
Agata Czarnywojtek ◽  
...  
Keyword(s):  
Immune Cell ◽  
Premature Menopause ◽  
Complex Disorders ◽  
Increased Risk ◽  
Organ Specific ◽  
Autoimmune Conditions ◽  
Cell Balance ◽  
Type 3 ◽  
Polyglandular Autoimmunity

Abstract Purpose Genetically predisposed individuals may develop several autoimmune diseases—autoimmune polyendocrine syndromes (APS). APS types 2–4, are complex disorders, which combine various organ-specific autoimmune conditions. Recent reports support the considerable role of the BACH2 gene in immune cell differentiation and shifting the T-cell balance towards regulatory T-cells. BACH2 polymorphisms are associated with autoimmune disorders, including Addison’s disease (AD), Graves’ disease (GD), and probably type 1 diabetes (T1D). Our study was aimed to investigate the BACH2 variant, rs3757247, in endocrine autoimmunity in the Polish population. Methods The analysis comprised 346 individuals with APS, 387 with T1D only, and 568 controls. Genotyping was performed using TaqMan chemistry. Results APS type 2 was found in 219 individuals, type 3 in 102, and type 4 in 25 subjects. Overall, AD was diagnosed in 244 subjects, Hashimoto’s thyroiditis—in 238, T1D—in 127, GD—in 58, vitiligo and chronic gastritis each in 40 patients, celiac disease—in 28, premature menopause in 18, and alopecia in 4 patients. Minor T allele at rs3757247 was found in 56.4% APS vs. 44.1% control alleles (OR 1.59; 95%CI: 1.30–1.95, p < 0.0001). The distribution of genotypes revealed excess TT homozygotes in the APS cohort (33.2 vs. 20.1% in controls, p < 0.0001). The frequencies of rs3757247 alleles and genotypes in T1D patients did not present significant differences vs. controls (p-values > 0.05). Conclusions These results provide evidence of the association between BACH2 polymorphism and polyglandular autoimmunity. Since carriers of rs3757247 display increased risk for additional autoimmune conditions, this variant could identify individuals prone to develop APS.

scholarly journals Essential role of IRAK-4 protein and its kinase activity in Toll-like receptor–mediated immune responses but not in TCR signaling

2007 ◽  
Vol 204 (5) ◽  
pp. 1013-1024 ◽  
Author(s):  
Tatsukata Kawagoe ◽  
Shintaro Sato ◽  
Andreas Jung ◽  
Masahiro Yamamoto ◽  
Kosuke Matsui ◽  
...  
Keyword(s):  
Immune Responses ◽  
Kinase Activity ◽  
Interleukin 1 ◽  
Cell Receptor ◽  
Nuclear Factor Κb ◽  
Toll Like Receptor ◽  
Tcr Signaling ◽  
Mitogen Activated Protein

Interleukin-1 receptor–associated kinase 4 (IRAK-4) was reported to be essential for the Toll-like receptor (TLR)– and T cell receptor (TCR)–mediated signaling leading to the activation of nuclear factor κB (NF-κB). However, the importance of kinase activity of IRAK family members is unclear. In this study, we investigated the functional role of IRAK-4 activity in vivo by generating mice carrying a knockin mutation (KK213AA) that abrogates its kinase activity. IRAK-4KN/KN mice were highly resistant to TLR-induced shock response. The cytokine production in response to TLR ligands was severely impaired in IRAK-4KN/KN as well as IRAK-4−/− macrophages. The IRAK-4 activity was essential for the activation of signaling pathways leading to mitogen-activated protein kinases. TLR-induced IRAK-4/IRAK-1–dependent and –independent pathways were involved in early induction of NF-κB–regulated genes in response to TLR ligands such as tumor necrosis factor α and IκBζ. In contrast to a previous paper (Suzuki, N., S. Suzuki, D.G. Millar, M. Unno, H. Hara, T. Calzascia, S. Yamasaki, T. Yokosuka, N.J. Chen, A.R. Elford, et al. 2006. Science. 311:1927–1932), the TCR signaling was not impaired in IRAK-4−/− and IRAK-4KN/KN mice. Thus, the kinase activity of IRAK-4 is essential for the regulation of TLR-mediated innate immune responses.

scholarly journals Molecular profiling demonstrates modulation of immune cell function and matrix remodeling during luteal rescue†

2019 ◽  
Vol 100 (6) ◽  
pp. 1581-1596 ◽  
Author(s):  
Camilla K Hughes ◽  
Samar W Maalouf ◽  
Wan-Sheng Liu ◽  
Joy L Pate
Keyword(s):  
Extracellular Matrix ◽  
Corpus Luteum ◽  
Cell Function ◽  
Immune Cell ◽  
Cell Receptor ◽  
Cytokine Signaling ◽  
Matrix Remodeling ◽  
Proteomic Profiling ◽  
Interferon Tau ◽  
In Pregnancy

Abstract The corpus luteum (CL) is essential for maintenance of pregnancy in all mammals and luteal rescue, which occurs around day 16–19 in the cow, is necessary to maintain luteal progesterone production. Transcriptomic and proteomic profiling were performed to compare the day 17 bovine CL of the estrous cycle and pregnancy. Among mRNA and proteins measured, 140 differentially abundant mRNA and 24 differentially abundant proteins were identified. Pathway analysis was performed using four programs. Modulated pathways included T cell receptor signaling, vascular stability, cytokine signaling, and extracellular matrix remodeling. Two mRNA that were less in pregnancy were regulated by prostaglandin F2A in culture, while two mRNA that were greater in pregnancy were regulated by interferon tau. To identify mRNA that could be critical regulators of luteal fate, the mRNA that were differentially abundant during early pregnancy were compared to mRNA that were differentially abundant during luteal regression. Eight mRNA were common to both datasets, including mRNA related to regulation of steroidogenesis and gene transcription. A subset of differentially abundant mRNA and proteins, including those associated with extracellular matrix functions, were predicted targets of differentially abundant microRNA (miRNA). Integration of miRNA and protein data, using miRPath, revealed pathways such as extracellular matrix–receptor interactions, abundance of glutathione, and cellular metabolism and energy balance. Overall, this study has provided a comprehensive profile of molecular changes in the corpus luteum during maternal recognition of pregnancy and has indicated that some of these functions may be miRNA-regulated.

scholarly journals Themis-associated phosphatase activity controls signaling in T cell development

2018 ◽  
Vol 115 (48) ◽  
pp. E11331-E11340 ◽  
Author(s):  
Monika Mehta ◽  
Joanna Brzostek ◽  
Elijah W. Chen ◽  
Desmond W. H. Tung ◽  
Shuting Chen ◽  
...  
Keyword(s):  
T Cell ◽  
Phosphatase Activity ◽  
Ex Vivo ◽  
Tyrosine Phosphatase ◽  
Cell Receptor ◽  
Conditional Knockout ◽  
Negative Regulator ◽  
Tcr Signaling ◽  
Thymic Development ◽  
Double Deletion

Thymocyte-expressed molecule involved in selection (Themis) has been shown to be important for T cell selection by setting the threshold for positive versus negative selection. Themis interacts with the protein tyrosine phosphatase (PTP) Src-homology domain containing phosphatase-1 (Shp1), a negative regulator of the T cell receptor (TCR) signaling cascade. However, how Themis regulates Shp1 is still not clear. Here, using a very sensitive phosphatase assay on ex vivo thymocytes, we have found that Themis enhances Shp1 phosphatase activity by increasing its phosphorylation. This positive regulation of Shp1 activity by Themis is found in thymocytes, but not in peripheral T cells. Shp1 activity is modulated by different affinity peptide MHC ligand binding in thymocytes. Themis is also associated with phosphatase activity, due to its constitutive interaction with Shp1. In the absence of Shp1 in thymocytes, Themis interacts with Shp2, which leads to almost normal thymic development in Shp1 conditional knockout (cKO) mice. Double deletion of both Themis and Shp1 leads to a thymic phenotype similar to that of Themis KO. These findings demonstrate unequivocally that Themis positively regulates Shp1 phosphatase activity in TCR-mediated signaling in developing thymocytes.

Nutritional Contributions to the CNS Pathophysiology of HIV-1 Infection and Implications for Treatment

CNS Spectrums ◽  
2000 ◽  
Vol 5 (4) ◽  
pp. 61-72 ◽  
Author(s):  
Teri T. Baldewicz ◽  
Pim Brouwers ◽  
Karl Goodkin ◽  
Adarsh M. Kumar ◽  
Mahendra Kumar
Keyword(s):  
Disease Progression ◽  
Causative Factor ◽  
Nutritional Deficiencies ◽  
Micronutrient Deficiencies ◽  
Increased Risk ◽  
Immunodeficiency Virus ◽  
Nutritional Deficits ◽  
Hiv 1

AbstractNutritional deficiencies are commonplace in patients with human immunodeficiency virus type 1 (HIV-1) infection, and recent research has indicated that nutritional factors may play an important role in the pathogenesis of HIV-1 disease. Although nutritional deficiencies are unlikely to be the primary causative factor in disease progression, they may contribute to cognitive dysfunction, neurologic abnormalities, mood disturbance, and immune dysregulation associated with HIV-1 infection. Furthermore, deficiencies of specific micronutrients have been associated with increased risk of HIV-1–associated mortality. This article will briefly summarize the role of macronutrient deficiency, the interactions of specific micronutrient deficiencies with neuropsychiatrie functioning, and the role of these factors in HIV-1 disease progression. Since recent research has shown that normalization of many nutritional deficits and supplementation beyond normal levels are associated with improvements in neuropsychiatrie functioning, potential treatment implications will also be discussed.

Sign in / Sign up

Export Citation Format

Share Document