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TCR signaling

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https://www.readbyqxmd.com/read/28930660/the-irf4-gene-regulatory-module-functions-as-a-read-write-integrator-to-dynamically-coordinate-t%C3%A2-helper-cell-fate
#1
Veena Krishnamoorthy, Sunil Kannanganat, Mark Maienschein-Cline, Sarah L Cook, Jianjun Chen, Neil Bahroos, Evelyn Sievert, Emily Corse, Anita Chong, Roger Sciammas
Transcriptional regulation during CD4(+) T cell fate decisions enables their differentiation into distinct states, guiding immune responses toward antibody production via Tfh cells or inflammation by Teff cells. Tfh-Teff cell fate commitment is regulated by mutual antagonism between the transcription factors Bcl6 and Blimp-1. Here we examined how T cell receptor (TCR) signals establish and arbitrate Bcl6-Blimp-1 counter-antagonism. We found that the TCR-signal-induced transcription factor Irf4 is essential for the differentiation of Bcl6-expressing Tfh and Blimp-1-expressing Teff cells...
September 19, 2017: Immunity
https://www.readbyqxmd.com/read/28928269/perturbed-cd8-t-cell-immunity-across-universal-influenza-epitopes-in-the-elderly
#2
Thi H O Nguyen, Sneha Sant, Nicola L Bird, Emma J Grant, E Bridie Clemens, Marios Koutsakos, Sophie A Valkenburg, Stephanie Gras, Martha Lappas, Anthony Jaworowski, Jane Crowe, Liyen Loh, Katherine Kedzierska
Influenza epidemics lead to severe illness, life-threatening complications, and deaths, especially in the elderly. As CD8(+) T cells are associated with rapid recovery from influenza, we investigated the effects of aging on antigen-specific CD8(+) T cells across the universal influenza epitopes in humans. We show that aging is characterized by altered frequencies in T cell subsets, with naive T cells being partially replaced by activated effector/memory populations. Although we observed no striking differences in TCR signaling capacity, T cells in the elderly had increased expression of transcription factors Eomes and T-bet, and such changes were most apparent in CD8(+) T cells...
September 19, 2017: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/28926770/1-25-oh-2d3-induces-regulatory-t-cell-differentiation-by-influencing-the-vdr-plc-%C3%AE-1-tgf-%C3%AE-1-pathway
#3
Qiang Zhou, Shengying Qin, Jinyan Zhang, Lin Zhon, Zhihai Pen, Tonghai Xing
Vitamin D has been recommended as an immune modulator in recent years, in addition to regulating calcium-phosphorous-bone metabolism. Clinical studies on organ transplantation found that vitamin D sufficiency patients were less likely to develop acute cellular rejection within one year after transplantation compared to those with vitamin D deficiency. Thus, a high percentage of regulatory T cells might play a key role in preventing acute cellular rejection (ACR). In this report, we studied the specific effects of 1,25(OH)2D3 on human T cell diff ;erentiation, and determined the potential molecule mechanism behind...
September 16, 2017: Molecular Immunology
https://www.readbyqxmd.com/read/28923982/emerging-concepts-in-tcr-specificity-rationalizing-and-maybe-predicting-outcomes
#4
REVIEW
Nishant K Singh, Timothy P Riley, Sarah Catherine B Baker, Tyler Borrman, Zhiping Weng, Brian M Baker
T cell specificity emerges from a myriad of processes, ranging from the biological pathways that control T cell signaling to the structural and physical mechanisms that influence how TCRs bind peptides and MHC proteins. Of these processes, the binding specificity of the TCR is a key component. However, TCR specificity is enigmatic: TCRs are at once specific but also cross-reactive. Although long appreciated, this duality continues to puzzle immunologists and has implications for the development of TCR-based therapeutics...
October 1, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28919076/mitochondrial-priming-by-cd28
#5
Ramon I Klein Geltink, David O'Sullivan, Mauro Corrado, Anna Bremser, Michael D Buck, Joerg M Buescher, Elke Firat, Xuekai Zhu, Gabriele Niedermann, George Caputa, Beth Kelly, Ursula Warthorst, Anne Rensing-Ehl, Ryan L Kyle, Lana Vandersarren, Jonathan D Curtis, Annette E Patterson, Simon Lawless, Katarzyna Grzes, Jing Qiu, David E Sanin, Oliver Kretz, Tobias B Huber, Sophie Janssens, Bart N Lambrecht, Angelika S Rambold, Edward J Pearce, Erika L Pearce
T cell receptor (TCR) signaling without CD28 can elicit primary effector T cells, but memory T cells generated during this process are anergic, failing to respond to secondary antigen exposure. We show that, upon T cell activation, CD28 transiently promotes expression of carnitine palmitoyltransferase 1a (Cpt1a), an enzyme that facilitates mitochondrial fatty acid oxidation (FAO), before the first cell division, coinciding with mitochondrial elongation and enhanced spare respiratory capacity (SRC). microRNA-33 (miR33), a target of thioredoxin-interacting protein (TXNIP), attenuates Cpt1a expression in the absence of CD28, resulting in cells that thereafter are metabolically compromised during reactivation or periods of increased bioenergetic demand...
September 1, 2017: Cell
https://www.readbyqxmd.com/read/28904128/integration-of-kinase-and-calcium-signaling-at-the-level-of-chromatin-underlies-inducible-gene-activation-in-t-cells
#6
Ruth Brignall, Pierre Cauchy, Sarah L Bevington, Bethany Gorman, Angela O Pisco, James Bagnall, Christopher Boddington, William Rowe, Hazel England, Kevin Rich, Lorraine Schmidt, Nigel P Dyer, Mark A Travis, Sascha Ott, Dean A Jackson, Peter N Cockerill, Pawel Paszek
TCR signaling pathways cooperate to activate the inducible transcription factors NF-κB, NFAT, and AP-1. In this study, using the calcium ionophore ionomycin and/or PMA on Jurkat T cells, we show that the gene expression program associated with activation of TCR signaling is closely related to specific chromatin landscapes. We find that calcium and kinase signaling cooperate to induce chromatin remodeling at ∼2100 chromatin regions, which demonstrate enriched binding motifs for inducible factors and correlate with target gene expression...
September 13, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28902773/reduced-tcr-signalling-contributes-to-impaired-th17-responses-in-tolerant-kidney-transplant-recipients
#7
Estefania Nova-Lamperti, Marco Romano, Sofia Christakoudi, Manohursingh Runglall, Reuben McGregor, Paula Mobillo, Yogesh Kamra, Tjir-Li Tsui, Sonia Norris, Susan John, Dominic A Boardman, Robert I Lechler, Giovanna Lombardi, Maria P Hernandez-Fuentes
BACKGROUND: The development of spontaneous kidney transplant tolerance has been associated with numerous B cell-related immune alterations. We have previously shown that tolerant recipients exhibit reduced B cell receptor (BCR) signalling and higher IL-10 production than healthy volunteers. However, it is unclear whether CD4T cells from tolerant recipients also display an antiinflammatory profile that could contribute to graft maintenance. METHODS: CD4T cells were isolated from kidney transplant recipients who were identified as being tolerant recipients, patients with chronic-rejection or healthy volunteers...
September 12, 2017: Transplantation
https://www.readbyqxmd.com/read/28900926/immunological-disorders-regulation-of-ca-2-signaling-in-t-lymphocytes
#8
Sonal Srikanth, Jin Seok Woo, Zuoming Sun, Yousang Gwack
Engagement of T cell receptors (TCRs) with cognate antigens triggers cascades of signaling pathways in helper T cells. TCR signaling is essential for the effector function of helper T cells including proliferation, differentiation, and cytokine production. It also modulates effector T cell fate by inducing cell death, anergy (nonresponsiveness), exhaustion, and generation of regulatory T cells. One of the main axes of TCR signaling is the Ca(2+)-calcineurin-nuclear factor of activated T cells (NFAT) signaling pathway...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/28900678/socs1-regulator-of-t-cells-in-autoimmunity-and-cancer
#9
Subburaj Ilangumaran, Diwakar Bobbala, Sheela Ramanathan
SOCS1 is a negative feedback regulator of cytokine and growth factor receptor signaling, and plays an indispensable role in attenuating interferon gamma signaling. Studies on SOCS1-deficient mice have established a crucial role for SOCS1 in regulating CD8(+) T cell homeostasis. In the thymus, SOCS1 prevents thymocytes that had failed positive selection from surviving and expanding, ensures negative selection and prevents inappropriate developmental skewing toward the CD8 lineage. In the periphery, SOCS1 not only controls production of T cell stimulatory cytokines but also attenuates the sensitivity of CD8(+) T cells to synergistic cytokine stimulation and antigen non-specific activation...
September 13, 2017: Current Topics in Microbiology and Immunology
https://www.readbyqxmd.com/read/28899359/transcript-profiling-of-the-immunological-interactions-between-actinobacillus-pleuropneumoniae-serotype-7-and-the-host-by-dual-rna-seq
#10
Ping Li, Zhiwen Xu, Xiangang Sun, Yue Yin, Yi Fan, Jun Zhao, Xiyu Mao, Jianbo Huang, Fan Yang, Ling Zhu
BACKGROUND: The complexity of the pathogenic mechanism underlying the host immune response to Actinobacillus pleuropneumonia (App) makes the use of preventive measures difficult, and a more global view of the host-pathogen interactions and new insights into this process are urgently needed to reveal the pathogenic and immune mechanisms underlying App infection. Here, we infected specific pathogen-free Mus musculus with App serotype 7 by intranasal inoculation to construct an acute hemorrhagic pneumonia infection model and isolated the infected lungs for analysis of the interactions by dual RNA-seq...
September 12, 2017: BMC Microbiology
https://www.readbyqxmd.com/read/28894001/intestinal-type-1-regulatory-t-cells-migrate-to-periphery-to-suppress-diabetogenic-t-cells-and-prevent-diabetes-development
#11
Hua Yu, Nicola Gagliani, Harumichi Ishigame, Samuel Huber, Shu Zhu, Enric Esplugues, Kevan C Herold, Li Wen, Richard A Flavell
Growing insight into the pathogenesis of autoimmune diseases and numerous studies in preclinical models highlights the potential of regulatory T cells to restore tolerance. By using non-obese diabetic (NOD) BDC2.5 TCR-transgenic (Tg), and IL-10 and Foxp3 double-reporter mice, we demonstrate that alteration of gut microbiota during cohousing experiments or treatment with anti-CD3 mAb significantly increase intestinal IL-10-producing type 1 regulatory T (Tr1) cells and decrease diabetes incidence. These intestinal antigen-specific Tr1 cells have the ability to migrate to the periphery via a variety of chemokine receptors such as CCR4, CCR5, and CCR7 and to suppress proliferation of Th1 cells in the pancreas...
September 11, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28893902/the-cytosolic-domain-of-t-cell-receptor-%C3%AE-associates-with-membranes-in-a-dynamic-equilibrium-and-deeply-penetrates-the-bilayer
#12
Kerstin Zimmermann, Rebecca Eells, Frank Heinrich, Stefanie Rintoul, Brian Josey, Prabhanshu Shekhar, Mathias Lösche, Lawrence J Stern
Interactions between lipid bilayers and the membrane-proximal regions of membrane-associated proteins play important roles in regulat-ing membrane protein structure and function. The T-cell antigen receptor (TCR) is an assembly of eight single-pass membrane-spanning subunits on the surface of T-lymphocytes that initiates cytosolic signaling cascades upon binding antigens presented by MHC-family proteins on antigen-presenting cells. Its ζ subunit contains multiple cytosolic immunoreceptor tyrosine-based activation motifs (ITAMs) involved in signal transduction, and this subunit by itself is sufficient to couple extracellular stimuli to intracellular signaling events...
September 11, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28891065/il4-induced-gene-1-is-secreted-at-the-immune-synapse-and-modulates-tcr-activation-independently-of-its-enzymatic-activity
#13
Aude Aubatin, Nouhoum Sako, Xavier Decrouy, Emmanuel Donnadieu, Valérie Molinier-Frenkel, Flavia Castellano
Amino-acid catabolizing enzymes produced by mononuclear phagocytes play a central role in regulating the immune response. The mammalian phenylalanine-catabolizing enzyme IL4-induced gene 1 (IL4I1) inhibits effector T lymphocyte proliferation and facilitates regulatory T-cell development. IL4I1 expression by macrophages of various human tumors may affect patient prognosis as it facilitates tumor escape from the T-cell response in murine models. Its enzymatic activity appears to participate in its effects, but some actions of IL4I1 remain unclear...
September 10, 2017: European Journal of Immunology
https://www.readbyqxmd.com/read/28889989/the-tnf-receptor-superfamily-nf-%C3%AE%C2%BAb-axis-is-critical-to-maintain-effector-regulatory-t-cells-in-lymphoid-and-non-lymphoid-tissues
#14
Ajithkumar Vasanthakumar, Yang Liao, Peggy Teh, Maria F Pascutti, Anna E Oja, Alexandra L Garnham, Renee Gloury, Jessica C Tempany, Tom Sidwell, Eloy Cuadrado, Paul Tuijnenburg, Taco W Kuijpers, Najoua Lalaoui, Lisa A Mielke, Vanessa L Bryant, Philip D Hodgkin, John Silke, Gordon K Smyth, Martijn A Nolte, Wei Shi, Axel Kallies
After exiting the thymus, Foxp3(+) regulatory T (Treg) cells undergo further differentiation in the periphery, resulting in the generation of mature, fully suppressive effector (e)Treg cells in a process dependent on TCR signaling and the transcription factor IRF4. Here, we show that tumor necrosis factor receptor superfamily (TNFRSF) signaling plays a crucial role in the development and maintenance of eTreg cells. TNFRSF signaling activated the NF-κB transcription factor RelA, which was required to maintain eTreg cells in lymphoid and non-lymphoid tissues, including RORγt(+) Treg cells in the small intestine...
September 19, 2017: Cell Reports
https://www.readbyqxmd.com/read/28889947/an-nf-%C3%AE%C2%BAb-transcription-factor-dependent-lineage-specific-transcriptional-program-promotes-regulatory-t-cell-identity-and-function
#15
Hyunju Oh, Yenkel Grinberg-Bleyer, Will Liao, Dillon Maloney, Pingzhang Wang, Zikai Wu, Jiguang Wang, Dev M Bhatt, Nicole Heise, Roland M Schmid, Matthew S Hayden, Ulf Klein, Raul Rabadan, Sankar Ghosh
Both conventional T (Tconv) cells and regulatory T (Treg) cells are activated through ligation of the T cell receptor (TCR) complex, leading to the induction of the transcription factor NF-κB. In Tconv cells, NF-κB regulates expression of genes essential for T cell activation, proliferation, and function. However the role of NF-κB in Treg function remains unclear. We conditionally deleted canonical NF-κB members p65 and c-Rel in developing and mature Treg cells and found they have unique but partially redundant roles...
September 19, 2017: Immunity
https://www.readbyqxmd.com/read/28878363/a-tcr-based-chimeric-antigen-receptor
#16
Even Walseng, Hakan Köksal, Ibrahim M Sektioglu, Anne Fåne, Gjertrud Skorstad, Gunnar Kvalheim, Gustav Gaudernack, Else Marit Inderberg, Sébastien Wälchli
Effector T cells equipped with engineered antigen receptors specific for cancer targets have proven to be very efficient. Two methods have emerged: the Chimeric Antigen Receptors (CARs) and T-cell Receptor (TCR) redirection. Although very potent, CAR recognition is limited to membrane antigens which represent around 1% of the total proteins expressed, whereas TCRs have the advantage of targeting any peptide resulting from cellular protein degradation. However, TCRs depend on heavy signalling machinery only present in T cells which restricts the type of eligible therapeutic cells...
September 6, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28878277/increased-tcr-signal-strength-in-dn-thymocytes-promotes-development-of-gut-tcr%C3%AE-%C3%AE-cd8%C3%AE-%C3%AE-intraepithelial-lymphocytes
#17
Capucine L Grandjean, Nital Sumaria, Stefania Martin, Daniel J Pennington
CD4((+))CD8((+)) "double positive" (DP) thymocytes differentiate into diverse αβ T cell sub-types using mechanistically distinct programs. For example, conventional αβ T cells develop from DP cells after partial-agonist T cell receptor (TCR) interactions with self-peptide/MHC, whereas unconventional αβ T cells, such as TCRαβ((+))CD8αα((+)) intraepithelial lymphocytes (IELs), require full-agonist TCR interactions. Despite this, DP cells appear homogeneous, and it remains unclear how distinct TCR signalling instructs distinct developmental outcomes...
September 6, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28877990/grb2-mediated-recruitment-of-usp9x-to-lat-enhances-themis-stability-following-thymic-selection
#18
Anne Garreau, Gaëtan Blaize, Jérémy Argenty, Nelly Rouquié, Audrey Tourdès, Stephen A Wood, Abdelhadi Saoudi, Renaud Lesourne
Themis is a new component of the TCR signaling machinery that plays a critical role during T cell development. The positive selection of immature CD4(+)CD8(+) double-positive thymocytes and their commitment to the CD4(+)CD8(-) single-positive stage are impaired in Themis(-/-) mice, suggesting that Themis might be important to sustain TCR signals during these key developmental processes. However, the analysis of Themis mRNA levels revealed that Themis gene expression is rapidly extinguished during positive selection...
September 6, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28877231/functional-characterization-of-t-cells-from-palatine-tonsils-in-patients-with-chronic-tonsillitis
#19
Katharina Geißler, Robby Markwart, Robert Pascal Requardt, Cynthia Weigel, Katja Schubert, André Scherag, Ignacio Rubio, Orlando Guntinas-Lichius
The palatine tonsils, localized in the oropharynx, are easily accessible secondary lymphoid tissue in humans. Inflammation of the palatine tonsils, local and chronic in case of chronic tonsillitis (CT) or acute in the presence of a peritonsillar abscess (PTA), ranks among the most common diseases in otolaryngology. However, the functionality of tonsillar immune cells, notably T-cells, in the context of these immune pathologies is poorly understood. We have examined the functional status of human tonsillar T-cells in CT and compared it to the acute inflammatory setting of a PTA...
2017: PloS One
https://www.readbyqxmd.com/read/28875488/transcriptional-regulation-of-t-cell-metabolism-reprograming
#20
Jinxia Zhang, Guoyu Bi, Yu Xia, Pingfei Li, Xiaofei Deng, Zhengping Wei, Xiang-Ping Yang
T cell activation, differentiation, and function are tightly regulated by a complex network of transcription factors, epigenetic modifications, and signaling pathways of both TCR and cytokines. Over the past decade, it is increasingly clear that T cell immune responses are also regulated by their associated metabolic reprograming. Compared with relatively well-understood transcriptional regulation of T cell activation, differentiation, and function, less is known about the transcriptional regulation of T cell metabolic reprograming during T cell immune responses...
2017: Advances in Experimental Medicine and Biology
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