scholarly journals Ndfip1 Protein Promotes the Function of Itch Ubiquitin Ligase to Prevent T Cell Activation and T Helper 2 Cell-Mediated Inflammation

Immunity ◽  
2006 ◽  
Vol 25 (6) ◽  
pp. 929-940 ◽  
Author(s):  
Paula M. Oliver ◽  
Xiao Cao ◽  
George Scott Worthen ◽  
Peijun Shi ◽  
Natalie Briones ◽  
...  
Keyword(s):  
T Cell ◽  
T Cell Activation ◽  
Ubiquitin Ligase ◽  
Cell Activation ◽  
T Helper ◽  
T Helper 2

scholarly journals CRL4-DCAF12 Ubiquitin Ligase Controls MOV10 RNA Helicase during Spermatogenesis and T Cell Activation

2021 ◽  
Vol 22 (10) ◽  
pp. 5394
Author(s):  
Tomas Lidak ◽  
Nikol Baloghova ◽  
Vladimir Korinek ◽  
Radislav Sedlacek ◽  
Jana Balounova ◽  
...  
Keyword(s):  
T Cell ◽  
T Cell Activation ◽  
Ubiquitin Ligase ◽  
Cell Activation ◽  
Rna Helicase ◽  
Dependent Manner ◽  
Amino Acid Residues ◽  
Risc Complex ◽  
Wide Range

Multisubunit cullin-RING ubiquitin ligase 4 (CRL4)-DCAF12 recognizes the C-terminal degron containing acidic amino acid residues. However, its physiological roles and substrates are largely unknown. Purification of CRL4-DCAF12 complexes revealed a wide range of potential substrates, including MOV10, an “ancient” RNA-induced silencing complex (RISC) complex RNA helicase. We show that DCAF12 controls the MOV10 protein level via its C-terminal motif in a proteasome- and CRL-dependent manner. Next, we generated Dcaf12 knockout mice and demonstrated that the DCAF12-mediated degradation of MOV10 is conserved in mice and humans. Detailed analysis of Dcaf12-deficient mice revealed that their testes produce fewer mature sperms, phenotype accompanied by elevated MOV10 and imbalance in meiotic markers SCP3 and γ-H2AX. Additionally, the percentages of splenic CD4+ T and natural killer T (NKT) cell populations were significantly altered. In vitro, activated Dcaf12-deficient T cells displayed inappropriately stabilized MOV10 and increased levels of activated caspases. In summary, we identified MOV10 as a novel substrate of CRL4-DCAF12 and demonstrated the biological relevance of the DCAF12-MOV10 pathway in spermatogenesis and T cell activation.

Procainamide-induced autoimmunity: Relationship to T-helper 2-type T-cell activation

2017 ◽  
Vol 37 (6) ◽  
pp. 647-662 ◽  
Author(s):  
Y Huang ◽  
Z Lin ◽  
Y Huo ◽  
X Geng ◽  
M Li ◽  
...  
Keyword(s):  
T Cell Activation ◽  
Cell Activation ◽  
Genetic Factors ◽  
Autoimmune Response ◽  
Brown Norway ◽  
T Helper ◽  
Sprague Dawley ◽  
Drug Induced ◽  
T Helper 2 ◽  
Toxicological Mechanism

Drug-induced autoimmunity (DIA) refers to a group of adverse drug reactions, and they remain unpredictable largely due to the limited understanding of the mechanisms involved. There is evidence that procainamide can cause autoimmune reactions in humans but the mechanisms involved remain unclear. To examine the cellular and genetic factors involved in the procainamide-induced autoimmune response, we compared rats that are genetically T-helper (Th)2-predisposed (Brown Norway (BN)), Th1-predisposed (Lewis (LEW)) or not genetically predisposed (Sprague Dawley (SD)). We revealed significant differences in response to autoimmunity induced by procainamide among three strains rats, BN was the most sensitive one, SD exhibited less sensitive, while LEW resistance to procainamide. Much more pronounced of Th2-type responses and more complex differentially expressed genes involved in immune regulation and response in BN might contribute to its susceptibleness to DIA. Moreover, similar immune mechanisms were found between BN and SD, which suggesting that these changes would serve as the potential bridge biomarkers to predict DIA among species. This study may also benefit to further understand the toxicological mechanism of drug-induced autoimmune reactions.

scholarly journals T Helper 17 Cells Promote Cytotoxic T Cell Activation in Tumor Immunity

Immunity ◽  
2009 ◽  
Vol 31 (5) ◽  
pp. 787-798 ◽  
Author(s):  
Natalia Martin-Orozco ◽  
Pawel Muranski ◽  
Yeonseok Chung ◽  
Xuexian O. Yang ◽  
Tomohide Yamazaki ◽  
...  
Keyword(s):  
T Cell ◽  
Tumor Immunity ◽  
T Cell Activation ◽  
Cell Activation ◽  
Cytotoxic T Cell ◽  
T Helper ◽  
T Helper 17 ◽  
T Helper 17 Cells

scholarly journals Regulation of the Interleukin (IL)-12R β2 Subunit Expression in Developing T Helper 1 (Th1) and Th2 Cells

1997 ◽  
Vol 185 (5) ◽  
pp. 817-824 ◽  
Author(s):  
Susanne J. Szabo ◽  
Anand S. Dighe ◽  
Ueli Gubler ◽  
Kenneth M. Murphy
Keyword(s):  
T Cell ◽  
T Cell Activation ◽  
Cell Activation ◽  
Th2 Cells ◽  
T Helper ◽  
T Helper 1 ◽  
Selective Loss ◽  
Th Cell ◽  
Subunit Expression ◽  
Ifn Γ

The developmental commitment to a T helper 1 (Th1)- or Th2-type response can significantly influence host immunity to pathogens. Extinction of the IL-12 signaling pathway during early Th2 development provides a mechanism that allows stable phenotype commitment. In this report we demonstrate that extinction of IL-12 signaling in early Th2 cells results from a selective loss of IL-12 receptor (IL-12R) β2 subunit expression. To determine the basis for this selective loss, we examined IL-12R β2 subunit expression during Th cell development in response to T cell treatment with different cytokines. IL-12R β2 is not expressed by naive resting CD4+ T cells, but is induced upon antigen activation through the T cell receptor. Importantly, IL-4 and IFN-γ were found to significantly modify IL-12 receptor β2 expression after T cell activation. IL-4 inhibited IL-12R β2 expression leading to the loss of IL-12 signaling, providing an important point of regulation to promote commitment to the Th2 pathway. IFN-γ treatment of early developing Th2 cells maintained IL-12R β2 expression and restored the ability of these cells to functionally respond to IL-12, but did not directly inhibit IL-4 or induce IFN-γ production. Thus, IFN-γ may prevent early Th cells from premature commitment to the Th2 pathway. Controlling the expression of the IL-12R β2 subunit could be an important therapeutic target for the redirection of ongoing Th cell responses.

scholarly journals Instruction for Cytokine Expression in T Helper Lymphocytes in Relation to Proliferation and Cell Cycle Progression

1999 ◽  
Vol 190 (10) ◽  
pp. 1439-1450 ◽  
Author(s):  
Anne Richter ◽  
Max Löhning ◽  
Andreas Radbruch
Keyword(s):  
Cell Cycle ◽  
T Cell ◽  
T Cell Activation ◽  
Cell Activation ◽  
Epigenetic Modification ◽  
S Phase ◽  
T Helper ◽  
Th Cells ◽  
Cytokine Genes ◽  
Tcr Signals

T helper (Th) lymphocytes, when reactivated, recall expression of those cytokines they had been instructed to express in earlier activations, even in the absence of specific cytokine-inducing factors. In cells that memorize their expression, the cytokine genes are modified by chromatin rearrangement and demethylation, suggesting that they have been somatically imprinted. Here we show, by using inhibitors blocking the cell cycle in various stages, that for the instruction of a Th cell to express interleukin (IL)-4 or IL-10 upon restimulation, entry of the cell into the S phase of the first cell cycle after initial activation is required. Separation of the IL-4 receptor (IL-4R) and T cell antigen receptor (TCR) signals in time, demonstrates that this instruction is dependent on concomitant signaling from both receptors. In Th cells, inhibited to progress into the first S phase after activation, the IL-4R and TCR signals can be memorized for at least 1 d, priming the T cell to become instructed for expression of IL-4 upon restimulation, when entering the S phase after release of the cell cycle block. The requirement of the initial S phase of T cell activation, for instruction of Th cells to express IL-4 or IL-10 upon restimulation points to the decisive role of epigenetic modification of cytokine genes as a molecular correlate of the memory to express particular cytokines.

Abstract P216: Inhibition Of T Cell Activation In Response To Placental Ischemia During Pregnancy Improves Hypertension And Activation Of Natural Killer Cells

Hypertension ◽  
2020 ◽  
Vol 76 (Suppl_1) ◽  
Author(s):  
Nathan Campbell ◽  
Evangeline M Deer ◽  
Lorena M Amaral ◽  
Kristen Reeve ◽  
Sarah Fitzgerald ◽  
...  
Keyword(s):  
Blood Pressure ◽  
T Cells ◽  
T Cell ◽  
Nk Cells ◽  
Natural Killer ◽  
T Cell Activation ◽  
T Helper Cells ◽  
Cell Activation ◽  
T Helper ◽  
Placental Ischemia

Preeclampsia (PE), new onset hypertension during pregnancy, is the leading cause of death and morbidity world-wide for the mother and fetus during pregnancy. The Reduced Uterine Perfusion Pressure Rat Model of PE (RUPP) exhibits many characteristics of PE including hypertension, suppressed regulatory T cells (T RegS ) associated with increased CD4+ T cells and B cells secreting agonistic autoantibodies to the AngII receptor (AT1-AA). We have previously shown that blockade of T-helper cells improves blood pressure and lowers AT1-AA secretion. A potential mechanism for the decreased blood pressure is decreased cytolytic natural killer (cNK) cells. Abatacept (Aba) is a fusion molecule designed to inhibit T cell co-stimulation in response to antigens and is used to treat autoimmune diseases. We hypothesize that treatment with Aba will prevent the activation of T-helper cells and therefore lower AT1-AA as a mechanism leading to less cNK cells in response to placental ischemia in RUPP rats. Aba was given on day 13 via the jugular vein. On day 19, blood and tissues were collected, blood pressure (MAP), pup weight, and NK cells were measured by flow cytometry in the blood and placenta. A one-way ANOVA was used for statistical analysis. On GD19, MAP significantly increased in RUPP 119±2 mmHg (n=7, p<0.05) compared to NP controls 102±2 mmHg (n=7) and was normalized with Aba (100±2 mmHg (n=10, p<0.05). Compared to the NP controls (2.2±0.06, n=7), pup weight significantly decreased in RUPP (2±0.08, n=7, p<0.05) but was 2± 0.07, with Aba (n=10). Circulating and placental total NK cells were 32±5, 44±13, % gate in NP rats (n=7), 59±4, 60±16 % gate in RUPP rats (n=7, p<0.05; n=4), which significantly decreased to 40±6, 28±8 % gate with Aba (n=10, p<0.05; n=11). Our findings indicate that prevention of T cell activation lowers total NK cell number and blood pressure in response to placental ischemia of pregnancy.

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