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https://www.readbyqxmd.com/read/29345428/traf3-regulation-of-inhibitory-signaling-pathways-in-b-and-t-lymphocytes-by-kinase-and-phosphatase-localization
#1
REVIEW
Alicia M Wallis, Gail A Bishop
This brief review presents current understanding of how the signaling adapter protein TRAF3 can both induce and block inhibitory signaling pathways in B and T lymphocytes, via association with kinases and phosphatases, and subsequent regulation of their localization within the cell. In B lymphocytes, signaling through the interleukin 6 receptor (IL-6R) induces association of TRAF3 with IL-6R-associated JAK1, to which TRAF3 recruits the phosphatase PTPN22 (protein tyrosine phosphatase number 22) to dephosphorylate JAK1 and STAT3, inhibiting IL-6R signaling...
January 17, 2018: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/29325864/infections-genetic-and-environmental-factors-in-pathogenesis-of-autoimmune-thyroid-diseases
#2
REVIEW
Sanjeev Kumar Shukla, Govind Singh, Shahzad Ahmad, Prabhat Pant
In Autoimmune disease a combination of infection, genetic and environmental factors causes an autoimmune response to the thyroid gland (characterized by lymphocytic infiltrations), thyroid stimulating hormone receptor (TSHR) and different thyroid antigens. Graves' and Hashimoto disease are autoimmune disorders with genetic predisposition. CD40 that stimulates the proliferation and differentiation of lymphocytes is an essential immunomodulatory component for follicular cells in the thyroid and the cell that present the antigen...
January 8, 2018: Microbial Pathogenesis
https://www.readbyqxmd.com/read/29310926/identification-of-non-hla-genes-associated-with-development-of-islet-autoimmunity-and-type-1-diabetes-in-the-prospective-teddy-cohort
#3
Ashok Sharma, Xiang Liu, David Hadley, William Hagopian, Wei-Min Chen, Suna Onengut-Gumuscu, Carina Törn, Andrea K Steck, Brigitte I Frohnert, Marian Rewers, Anette-G Ziegler, Åke Lernmark, Jorma Toppari, Jeffrey P Krischer, Beena Akolkar, Stephen S Rich, Jin-Xiong She
Traditional linkage analysis and genome-wide association studies have identified HLA and a number of non-HLA genes as genetic factors for islet autoimmunity (IA) and type 1 diabetes (T1D). However, the relative risk associated with previously identified non-HLA genes is usually very small as measured in cases/controls from mixed populations. Genetic associations for IA and T1D may be more accurately assessed in prospective cohorts. In this study, 5806 subjects from the TEDDY (The Environmental Determinants of Diabetes in the Young) study, an international prospective cohort study, were genotyped for 176,586 SNPs on the ImmunoChip...
January 5, 2018: Journal of Autoimmunity
https://www.readbyqxmd.com/read/29306244/tnf-alpha-863c-a-promoter-and-tnfrii-196t-g-exonic-variationsmay-be-risk-factors-for-juvenile-idiopathic-arthritis
#4
Bahadır Batar, Sezen Özman, Kenan Barut, Özgür Kasapçopur, Mehmet Güven
Background/aim: Juvenile idiopathic arthritis (JIA) is a chronic complex autoimmune disease. Genetic and environmental factors increase the risk of JIA. It is accepted that alterations in immune system pathways play an important role in the pathogenesis of JIA. The aim of the study was to investigate the possible association between immune system regulatory gene polymorphisms and JIA in Turkish patients. Materials and methods: We analyzed eight polymorphisms, TNF-alpha-863 C > A, TNFRII 196 T > G, IL2-631 G > A, IL13-1112 C > T, CCR2 190 G > A, CCR5delta32, CTLA4-1661 A > G, and PTPN22 1858 C > T, in 76 patients with JIA and in 80 healthy controls, who were of a similar age and same sex...
December 19, 2017: Turkish Journal of Medical Sciences
https://www.readbyqxmd.com/read/29251774/altered-toll-like-receptor-responsiveness-underlies-a-dominant-heritable-defect-in-b-cell-tolerance-in-autoimmune-new-zealand-black-mice
#5
Amy G Clark, Elizabeth S Buckley, Mary H Foster
Systemic lupus erythematosus is a debilitating autoimmune disease in which autoantibodies and autoreactive T cells destroy kidneys and other organs. Disease is clinically and genetically heterogeneous, suggesting that underlying mechanisms vary between patients. We previously used an autoantibody transgenic mouse reporter system to examine the effect of different autoimmune backgrounds on B-cell tolerance, failure of which is a fundamental defect in lupus. We identified a defect consistent with reversible anergy induced by endotoxin stimulation of B cells from Ig transgenic New Zealand Black (NZB) mice...
December 18, 2017: European Journal of Immunology
https://www.readbyqxmd.com/read/29183848/combinational-sirna-delivery-using-hyaluronic-acid-modified-amphiphilic-polyplexes-against-cell-cycle-and-phosphatase-proteins-to-inhibit-growth-and-migration-of-triple-negative-breast-cancer-cells
#6
Manoj B Parmar, Daniel Nisakar Meenakshi Sundaram, Kc Remant Bahadur, Robert Maranchuk, Hamidreza Montazeri Aliabadi, Judith C Hugh, Raimar Löbenberg, Hasan Uludağ
Triple-negative breast cancer is an aggressive form of breast cancer with few therapeutic options if it recurs after adjuvant chemotherapy. RNA interference could be an alternative therapy for metastatic breast cancer, where small interfering RNA (siRNA) can silence the expression of aberrant genes critical for growth and migration of malignant cells. Here, we formulated a siRNA delivery system using lipid-substituted polyethylenimine (PEI) and hyaluronic acid (HA), and characterized the size, ζ-potential and cellular uptake of the nanoparticulate delivery system...
November 25, 2017: Acta Biomaterialia
https://www.readbyqxmd.com/read/29120582/role-of-ptpn22-1858-c-t-polymorphisms-in-juvenile-idiopathic-arthritis-in-egyptian-patients
#7
Yasser A Soliman, Nashwa I Hashaad, Sherin M Emam, Rehab R Mohamed
Juvenile idiopathic arthritis (JIA) the most common chronic arthropathy of childhood is a diverse group of chronic arthritis diseases. The protein tyrosine phosphatase N22 (PTPN22) gene exhibits regulatory activities for both T and B cells. This study aimed to study PTPN gene polymorphism in JIA. The study included 60 children with JIA and 40 age and sex matched healthy children as controls. Patients and control groups were subjected to PTPN gene polymorphism analysis. Our findings indicated a significant difference in PTPN22 polymorphism between JIA patients and the control group (P = 0...
January 2017: Egyptian Journal of Immunology
https://www.readbyqxmd.com/read/29116089/resistance-to-tgf%C3%AE-suppression-and-improved-anti-tumor-responses-in-cd8-t-cells-lacking-ptpn22
#8
Rebecca J Brownlie, Celine Garcia, Mate Ravasz, Dietmar Zehn, Robert J Salmond, Rose Zamoyska
Transforming growth factor β (TGFβ) is important in maintaining self-tolerance and inhibits T cell reactivity. We show that CD8(+) T cells that lack the tyrosine phosphatase Ptpn22, a major predisposing gene for autoimmune disease, are resistant to the suppressive effects of TGFβ. Resistance to TGFβ suppression, while disadvantageous in autoimmunity, helps Ptpn22 (-/-) T cells to be intrinsically superior at clearing established tumors that secrete TGFβ. Mechanistically, loss of Ptpn22 increases the capacity of T cells to produce IL-2, which overcomes TGFβ-mediated suppression...
November 7, 2017: Nature Communications
https://www.readbyqxmd.com/read/29105157/reduced-numbers-of-mature-medullary-thymic-epithelial-cells-in-skg-mice
#9
Robby Engelmann, Andra Biemelt, Anja Johl, Daniela Kuthning, Brigitte Müller-Hilke
Attenuated T cell receptor (TCR) signaling contributes to the susceptibility for autoimmunity as shown via mutants of PTPN22 and Zap70 genes. We here set out to investigate the effect of an attenuated TCR signal on the composition of the thymic epithelial cell (TEC) compartment. To that extent, we combined flow cytometry and histology and compared the TEC subpopulations of Zap70 wild type with SKG mutant mice. We found an increased cortical TEC compartment in SKG thymi at the expense of reduced numbers of mature medullary TECs and a 4...
November 3, 2017: Scandinavian Journal of Immunology
https://www.readbyqxmd.com/read/29099700/-study-of-the-ptpn22-gene-in-children-with-type-1-diabetes-mellitus-in-the-azerbaijani-population
#10
G Ahmadov
The PTPN22 gene was studied in 160 children with type 1 diabetes mellitus under the age of 18 years and in 271 healthy children. Of the 160 patients, 50.6% (n=81) were boys, 49.4% (n=79) were girls. The average age of diabetic children was 9.1 years. The survey was conducted on the basis of the Children's Clinical Hospital No. 6 in Baku city. For all patients, a special questionnaire was filled out. Only children of Azerbaijani nationality were included in the study. As a comparison group, 271 students of the Medical College No...
October 2017: Georgian Medical News
https://www.readbyqxmd.com/read/29040339/protein-tyrosine-phosphatase-ptpn22-is-dispensable-for-dendritic-cell-antigen-processing-and-promotion-of-t-cell-activation-by-dendritic-cells
#11
Fiona Clarke, Christine K Jordan, Enrique Gutiérrez-Martinez, Jack A Bibby, Cristina Sanchez-Blanco, Georgina H Cornish, Xuezhi Dai, David J Rawlings, Rose Zamoyska, Pierre Guermonprez, Andrew P Cope, Harriet A Purvis
The PTPN22R620W single nucleotide polymorphism increases the risk of developing multiple autoimmune diseases including type 1 diabetes, rheumatoid arthritis and lupus. PTPN22 is highly expressed in antigen presenting cells (APCs) where the expression of the murine disease associated variant orthologue (Ptpn22R619W) is reported to dysregulate pattern recognition receptor signalling in dendritic cells (DCs) and promote T-cell proliferation. Because T-cell activation is dependent on DC antigen uptake, degradation and presentation, we analysed the efficiency of these functions in splenic and GM-CSF bone marrow derived DC from wild type (WT), Ptpn22-/- or Ptpn22R619W mutant mice...
2017: PloS One
https://www.readbyqxmd.com/read/29029456/protein-tyrosine-phosphatase-nonreceptor-type-22-ptpn22-gene-single-nucleotide-polymorphisms-and-its-interaction-with-t2dm-on-pulmonary-tuberculosis-in-chinese-uygur-population
#12
Xian-Hua Wang, Ai-Guo Ma, Xiu-Xia Han, Lei Chen, Hui Liang, Aishan-Litifu, Abudumijit-Ablez, Feng Xue
AIMS: To investigate the association of several single nucleotide polymorphisms (SNPs) within Protein tyrosine phosphatase nonreceptor type 22 (PTPN22) gene and additional gene- gene and gene- type 2 diabetes mellitus (T2DM) interaction with pulmonary tuberculosis (PTB) risk in Chinese Uygur population. METHODS: A total of 722 participants (186 males, 536 females) were selected, including 360 PTB patients and 362 control participants. Generalized multifactor dimensionality reduction (GMDR) was used to screen the best interaction combination among SNPs and T2DM...
September 12, 2017: Oncotarget
https://www.readbyqxmd.com/read/28990435/ptpn22-1858c%C3%A2-%C3%A2-t-polymorphism-and-susceptibility-to-systemic-lupus-erythematosus-a-meta-analysis-update
#13
Suelen Cristina de Lima, José Eduardo Adelino, Sergio Crovella, Jaqueline de Azevedo Silva, Paula Sandrin-Garcia
Studies performed in the past years showed PTNP22 1858 C > T (rs2476601) polymorphism as associated with systemic lupus erythematosus susceptibility, although conflicting findings are still found. In this context, a powerful statistical study, such as meta-analysis, is necessary to establish a consensus. The aim of this study was to evaluate association studies between the PTPN22 1858 C > T polymorphism and SLE by a meta-analysis update, including three recently published studies in the last three years...
October 8, 2017: Autoimmunity
https://www.readbyqxmd.com/read/28977867/hdac10-promotes-angiogenesis-in-endothelial-cells-through-the-ptpn22-erk-axis
#14
Baoyu Duan, Dan Ye, Songcheng Zhu, Wenwen Jia, Chenqi Lu, Guiying Wang, Xudong Guo, Yangyang Yu, Chuanyue Wu, Jiuhong Kang
Angiogenesis is crucially involved in many physiological and pathological processes including tumor growth, but the molecular mechanisms regulating angiogenesis are incompletely understood. In this study, we investigated the functions and mechanism of histone deacetylase 10 (HDAC10), a member of the HDAC II family, in regulation of angiogenesis. HDAC10 overexpression in human umbilical vein endothelial cells (HUVECs) promoted tube formation, whereas depletion of HDAC10 from HUVECs inhibited tube formation in vitro and in vivo...
September 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/28977835/association-of-stat4-and-ptpn22-polymorphisms-and-their-interactions-with-type-1-autoimmune-hepatitis-susceptibility-in-chinese-han-children
#15
Xiaofeng Li, Huiqin Chen, Yun Cai, Pingping Zhang, Zhuanggui Chen
AIMS: To investigate the impact of signal transducer and activator of transcription 4 (STAT4) and the protein tyrosine phosphatase N22 (PTPN22) gene single nucleotide polymorphisms (SNPs), gene-gene interactions and haplotype on type-1 Autoimmune Hepatitis (AIH) risk. RESULTS: Logistic regression analysis showed that type 1 AIH was significantly higher in carriers of T allele of rs7574865 than those with GG genotype (P- value less than 0.001), higher in carriers of C allele of rs7582694 than those with GG genotype (P- value < 0...
September 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/28948613/protein-tyrosine-phosphatase-ptpn22-regulates-il-1%C3%AE-dependent-th17-responses-by-modulating-dectin-1-signaling-in-mice
#16
Harriet A Purvis, Fiona Clarke, Christine K Jordan, Cristina Sanchez Blanco, Georgina H Cornish, Xuezhi Dai, David J Rawlings, Rose Zamoyska, Andrew P Cope
A single nucleotide polymorphism within the PTPN22 gene is a strong genetic risk factor predisposing to the development of multiple autoimmune diseases. PTPN22 regulates Syk and Src family kinases downstream of immuno-receptors. Fungal β-glucan receptor dectin-1 signals via Syk, and dectin-1 stimulation induces arthritis in mouse models. We investigated whether PTPN22 regulates dectin-1 dependent immune responses. Bone marrow derived dendritic cells (BMDCs) generated from C57BL/6 wild type (WT) and Ptpn22(-/-) mutant mice, were pulsed with OVA323-339 and the dectin-1 agonist curdlan and co-cultured in vitro with OT-II T-cells or adoptively transferred into OT-II mice, and T-cell responses were determined by immunoassay...
September 25, 2017: European Journal of Immunology
https://www.readbyqxmd.com/read/28922436/genetic-risk-factors-for-autoimmune-thyroid-disease-might-affect-the-susceptibility-to-and-modulate-the-progression-of-primary-biliary-cholangitis
#17
Aleksander Kuś, Magdalena Arłukowicz-Grabowska, Konrad Szymański, Ewa Wunsch, Małgorzata Milkiewicz, Rafał Płoski, Zakera Shums, Gary L Norman, Piotr Milkiewicz, Tomasz Bednarczuk, Marcin Krawczyk
BACKGROUND AND AIMS: Patients with primary biliary cholangitis (PBC) frequently suffer from extrahepatic autoimmune conditions, of which autoimmune thyroid disease (AITD) is one of the most common. Previous studies identified several genetic variants increasing the odds of developing AITD. Here we investigate whether AITD-associated polymorphisms might also play a role in the development and clinical course of PBC and PBC associated with AITD (PBC-AITD). METHODS: To this end, we prospectively recruited 230 patients with PBC and 421 healthy controls...
September 2017: Journal of Gastrointestinal and Liver Diseases: JGLD
https://www.readbyqxmd.com/read/28874816/protein-tyrosine-phosphatase-non-receptor-22-and-c-src-tyrosine-kinase-genes-are-down-regulated-in-patients-with-rheumatoid-arthritis
#18
Sara Remuzgo-Martínez, Fernanda Genre, Santos Castañeda, Alfonso Corrales, Pablo Moreno-Fresneda, Begoña Ubilla, Verónica Mijares, Virginia Portilla, Jesús González-Vela, Trinitario Pina, Gonzalo Ocejo-Vinyals, Juan Irure-Ventura, Ricardo Blanco, Javier Martín, Javier Llorca, Raquel López-Mejías, Miguel A González-Gay
Several protein tyrosine phosphatase non-receptor 22 (PTPN22) single-nucleotide polymorphisms (SNPs) have been significantly related with rheumatoid arthritis (RA) susceptibility. Nevertheless, its potential influence on PTPN22 expression in RA has not been completely elucidated. Furthermore, PTPN22 binds to C-Src tyrosine kinase (CSK) forming a key complex in autoimmunity. However, the information of CSK gene in RA is scarce. In this study, we analyzed the relative PTPN22 and CSK expression in peripheral blood from 89 RA patients and 43 controls to determine if the most relevant PTPN22 (rs2488457, rs2476601 and rs33996649) and CSK (rs34933034 and rs1378942) polymorphisms may influence on PTPN22 and CSK expression in RA...
September 5, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28801357/the-autoimmune-risk-variant-ptpn22-c1858t-alters-b-cell-tolerance-at-discrete-checkpoints-and-differentially-shapes-the-naive-repertoire
#19
Genita Metzler, Xuezhi Dai, Christopher D Thouvenel, Socheath Khim, Tania Habib, Jane H Buckner, David J Rawlings
A common genetic variant in the gene encoding the protein tyrosine phosphatase nonreceptor type 22 (PTPN22 C1858T) has been linked to a wide range of autoimmune disorders. Although a B cell-intrinsic role in promoting disease has been reported, the mechanism(s) through which this variant functions to alter the preimmune B cell repertoire remains unknown. Using a series of polyclonal and transgenic self-reactive models harboring the analogous mutation in murine Ptpn22, we show evidence for enhanced BCR, B cell-activating factor receptor, and CD40 coreceptor programs, leading to broadly enhanced positive selection of B cells at two discrete checkpoints in the bone marrow and spleen...
October 1, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28777869/-progress-in-genetic-research-on-psoriatic-arthritis
#20
Yan Ju, Erle Dang, Chunxiang Yang, Hongping Song
Psoriatic arthritis is a form of inflammatory arthritis found among patients with psoriasis, which can lead to pain, swelling or stiffness in one or more joints and even movement disorders. Epidemiological studies have shown a higher heritability for psoriatic arthritis compared with psoriasis vulgaris. With the evolvement of DNA sequencing, many genes have been associated with psoriasis vulgaris and psoriatic arthritis, which included MHC, TNF, LCE, IL23R, IL12B, TRAF3IP2 and TNFAIP3, though some, such as MHC, IL-13 and PTPN22, have been specifically associated with psoriatic arthritis...
August 10, 2017: Zhonghua Yi Xue Yi Chuan Xue za Zhi, Zhonghua Yixue Yichuanxue Zazhi, Chinese Journal of Medical Genetics
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