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Blimp1 t cell

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https://www.readbyqxmd.com/read/28723546/local-modulation-of-antigen-presenting-cell-development-after-resolution-of-pneumonia-induces-long-term-susceptibility-to-secondary-infections
#1
Antoine Roquilly, Hamish E G McWilliam, Cedric Jacqueline, Zehua Tian, Raphael Cinotti, Marie Rimbert, Linda Wakim, Irina Caminschi, Mireille H Lahoud, Gabrielle T Belz, Axel Kallies, Justine D Mintern, Karim Asehnoune, Jose A Villadangos
Lung infections cause prolonged immune alterations and elevated susceptibility to secondary pneumonia. We found that, after resolution of primary viral or bacterial pneumonia, dendritic cells (DC), and macrophages exhibited poor antigen-presentation capacity and secretion of immunogenic cytokines. Development of these "paralyzed" DCs and macrophages depended on the immunosuppressive microenvironment established upon resolution of primary infection, which involved regulatory T (Treg) cells and the cytokine TGF-β...
July 18, 2017: Immunity
https://www.readbyqxmd.com/read/28701508/prdm1-regulates-thymic-epithelial-function-to-prevent-autoimmunity
#2
Natalie A Roberts, Brian D Adams, Nicholas I McCarthy, Reuben M Tooze, Sonia M Parnell, Graham Anderson, Susan M Kaech, Valerie Horsley
Autoimmunity is largely prevented by medullary thymic epithelial cells (TECs) through their expression and presentation of tissue-specific Ags to developing thymocytes, resulting in deletion of self-reactive T cells and supporting regulatory T cell development. The transcription factor Prdm1 has been implicated in autoimmune diseases in humans through genome-wide association studies and in mice using cell type-specific deletion of Prdm1 in T and dendritic cells. In this article, we demonstrate that Prdm1 functions in TECs to prevent autoimmunity in mice...
July 12, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28652395/differential-requirements-for-tcf1-long-isoforms-in-cd8-and-cd4-t-cell-responses-to-acute-viral-infection
#3
Jodi A Gullicksrud, Fengyin Li, Shaojun Xing, Zhouhao Zeng, Weiqun Peng, Vladimir P Badovinac, John T Harty, Hai-Hui Xue
In response to acute viral infection, activated naive T cells give rise to effector T cells that clear the pathogen and memory T cells that persist long-term and provide heightened protection. T cell factor 1 (Tcf1) is essential for several of these differentiation processes. Tcf1 is expressed in multiple isoforms, with all isoforms sharing the same HDAC and DNA-binding domains and the long isoforms containing a unique N-terminal β-catenin-interacting domain. In this study, we specifically ablated Tcf1 long isoforms in mice, while retaining expression of Tcf1 short isoforms...
June 26, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28615725/transcriptome-analysis-reveals-similarities-between-human-blood-cd3-cd56-bright-cells-and-mouse-cd127-innate-lymphoid-cells
#4
David S J Allan, Ana Sofia Cerdeira, Anuisa Ranjan, Christina L Kirkham, Oscar A Aguilar, Miho Tanaka, Richard W Childs, Cynthia E Dunbar, Jack L Strominger, Hernan D Kopcow, James R Carlyle
For many years, human peripheral blood natural killer (NK) cells have been divided into functionally distinct CD3(-) CD56(bright) CD16(-) and CD3(-) CD56(dim) CD16(+) subsets. Recently, several groups of innate lymphoid cells (ILC), distinct from NK cells in development and function, have been defined in mouse. A signature of genes present in mouse ILC except NK cells, defined by Immunological Genome Project studies, is significantly over-represented in human CD56(bright) cells, by gene set enrichment analysis...
June 14, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28586108/bcl6-promotes-follicular-helper-t-cell-differentiation-and-pd-1-expression-in-a-blimp1-independent-manner-in-mice
#5
Markus M Xie, Byung-Hee Koh, Kristin Hollister, Hao Wu, Jie Sun, Mark H Kaplan, Alexander L Dent
The transcription factors Bcl6 and Blimp1 have opposing roles in the development of the follicular helper T (TFH ) cells: Bcl6 promotes and Blimp1 inhibits TFH -cell differentiation. Similarly, Bcl6 activates, while Blimp1 represses, expression of the TFH -cell marker PD-1. However, Bcl6 and Blimp1 repress each other's expression, complicating the interpretation of the regulatory network. Here we sought to clarify the extent to which Bcl6 and Blimp1 independently control TFH -cell differentiation by generating mice with T-cell specific deletion of both Bcl6 and Blimp1 (double conditional KO [dcKO] mice)...
July 2017: European Journal of Immunology
https://www.readbyqxmd.com/read/28412245/cxcr5-cd8-t-cells-infiltrate-the-colorectal-tumors-and-nearby-lymph-nodes-and-are-associated-with-enhanced-igg-response-in-b-cells
#6
Junjie Xing, Chenxin Zhang, Xiaohong Yang, Shaoxuan Wang, Zhongchuan Wang, Xu Li, Enda Yu
Colorectal cancer is the third most prevalent cancer type worldwide and contributes to a significant percentage of cancer-related mortality. Recent studies have shown that the CXCR5(+)CD8(+) T cells present more potent proinflammatory function than CXCR5(-)CD8(+) T cells in chronic virus infections and in follicular lymphoma, but the role of CXCR5(+)CD8(+) T cells in colorectal cancer is yet unclear. In this study, we demonstrated that CXCR5(+)CD8(+) T cells were very rare in peripheral blood mononuclear cells from healthy and colorectal cancer individuals, but were significantly enriched in resected tumors and tumor-associated lymph nodes...
April 13, 2017: Experimental Cell Research
https://www.readbyqxmd.com/read/28322735/stella-collaborates-in-distinct-mesendodermal-cell-subpopulations-at-the-fetal-placental-interface-in-the-mouse-gastrula
#7
Adam D Wolfe, Adriana M Rodriguez, Karen M Downs
The allantois-derived umbilical component of the chorio-allantoic placenta shuttles fetal blood to and from the chorion, thereby ensuring fetal-maternal exchange. The progenitor populations that establish and supply the fetal-umbilical interface lie, in part, within the base of the allantois, where the germ line is claimed to segregate from the soma. Results of recent studies in the mouse have reported that STELLA (DPPA-3, PGC7) co-localizes with PRDM1 (BLIMP1), the bimolecular signature of putative primordial germ cells (PGCs) throughout the fetal-placental interface...
May 1, 2017: Developmental Biology
https://www.readbyqxmd.com/read/28314753/transethnic-meta-analysis-identifies-gsdma-and-prdm1-as-susceptibility-genes-to-systemic-sclerosis
#8
Chikashi Terao, Takahisa Kawaguchi, Philippe Dieude, John Varga, Masataka Kuwana, Marie Hudson, Yasushi Kawaguchi, Marco Matucci-Cerinic, Koichiro Ohmura, Gabriela Riemekasten, Aya Kawasaki, Paolo Airo, Tetsuya Horita, Akira Oka, Eric Hachulla, Hajime Yoshifuji, Paola Caramaschi, Nicolas Hunzelmann, Murray Baron, Tatsuya Atsumi, Paul Hassoun, Takeshi Torii, Meiko Takahashi, Yasuharu Tabara, Masakazu Shimizu, Akiko Tochimoto, Naho Ayuzawa, Hidetoshi Yanagida, Hiroshi Furukawa, Shigeto Tohma, Minoru Hasegawa, Manabu Fujimoto, Osamu Ishikawa, Toshiyuki Yamamoto, Daisuke Goto, Yoshihide Asano, Masatoshi Jinnin, Hirahito Endo, Hiroki Takahashi, Kazuhiko Takehara, Shinichi Sato, Hironobu Ihn, Soumya Raychaudhuri, Katherine Liao, Peter Gregersen, Naoyuki Tsuchiya, Valeria Riccieri, Inga Melchers, Gabriele Valentini, Anne Cauvet, Maria Martinez, Tsuneyo Mimori, Fumihiko Matsuda, Yannick Allanore
OBJECTIVES: Systemic sclerosis (SSc) is an autoimmune disease characterised by skin and systemic fibrosis culminating in organ damage. Previous genetic studies including genome-wide association studies (GWAS) have identified 12 susceptibility loci satisfying genome-wide significance. Transethnic meta-analyses have successfully expanded the list of susceptibility genes and deepened biological insights for other autoimmune diseases. METHODS: We performed transethnic meta-analysis of GWAS in the Japanese and European populations, followed by a two-staged replication study comprising a total of 4436 cases and 14 751 controls...
June 2017: Annals of the Rheumatic Diseases
https://www.readbyqxmd.com/read/28150777/pathologically-expanded-peripheral-t-helper-cell-subset-drives-b-cells-in-rheumatoid-arthritis
#9
Deepak A Rao, Michael F Gurish, Jennifer L Marshall, Kamil Slowikowski, Chamith Y Fonseka, Yanyan Liu, Laura T Donlin, Lauren A Henderson, Kevin Wei, Fumitaka Mizoguchi, Nikola C Teslovich, Michael E Weinblatt, Elena M Massarotti, Jonathan S Coblyn, Simon M Helfgott, Yvonne C Lee, Derrick J Todd, Vivian P Bykerk, Susan M Goodman, Alessandra B Pernis, Lionel B Ivashkiv, Elizabeth W Karlson, Peter A Nigrovic, Andrew Filer, Christopher D Buckley, James A Lederer, Soumya Raychaudhuri, Michael B Brenner
CD4(+) T cells are central mediators of autoimmune pathology; however, defining their key effector functions in specific autoimmune diseases remains challenging. Pathogenic CD4(+) T cells within affected tissues may be identified by expression of markers of recent activation. Here we use mass cytometry to analyse activated T cells in joint tissue from patients with rheumatoid arthritis, a chronic immune-mediated arthritis that affects up to 1% of the population. This approach revealed a markedly expanded population of PD-1(hi)CXCR5(-)CD4(+) T cells in synovium of patients with rheumatoid arthritis...
February 1, 2017: Nature
https://www.readbyqxmd.com/read/28149882/simian-immunodeficiency-virus-confounds-t-follicular-helper-t-cells-and-the-germinal-centre
#10
COMMENT
Tom N Lea-Henry, Simon H Jiang
Yamamoto et al. have studied T follicular helper (TFH) and germinal centre (GC) responses after infection of rhesus macaques (RM) infected with simian immunodeficiency virus (SIV). In this study the authors examined the behaviour of TFH, reproducing infection-associated TFH accumulation and their association with the quality of antibody responses against cross-clade viral epitopes. The authors correlate TFHIL4 and CD154 expression with superior antibody responses. Accumulation of TFH was accompanied by aberrant expression of non-TFH transcriptional regulators such as BLIMP1 in TFH, suggesting viral induced abnormalities may affect TFH function...
December 2016: Annals of Translational Medicine
https://www.readbyqxmd.com/read/27487330/cxcr5-follicular-cytotoxic-t-cells-control-viral-infection-in-b-cell-follicles
#11
Yew Ann Leong, Yaping Chen, Hong Sheng Ong, Di Wu, Kevin Man, Claire Deleage, Martina Minnich, Benjamin J Meckiff, Yunbo Wei, Zhaohua Hou, Dimitra Zotos, Kevin A Fenix, Anurag Atnerkar, Simon Preston, Jeffrey G Chipman, Greg J Beilman, Cody C Allison, Lei Sun, Peng Wang, Jiawei Xu, Jesse G Toe, Hao K Lu, Yong Tao, Umaimainthan Palendira, Alexander L Dent, Alan L Landay, Marc Pellegrini, Iain Comerford, Shaun R McColl, Timothy W Schacker, Heather M Long, Jacob D Estes, Meinrad Busslinger, Gabrielle T Belz, Sharon R Lewin, Axel Kallies, Di Yu
During unresolved infections, some viruses escape immunological control and establish a persistant reservoir in certain cell types, such as human immunodeficiency virus (HIV), which persists in follicular helper T cells (TFH cells), and Epstein-Barr virus (EBV), which persists in B cells. Here we identified a specialized group of cytotoxic T cells (TC cells) that expressed the chemokine receptor CXCR5, selectively entered B cell follicles and eradicated infected TFH cells and B cells. The differentiation of these cells, which we have called 'follicular cytotoxic T cells' (TFC cells), required the transcription factors Bcl6, E2A and TCF-1 but was inhibited by the transcriptional regulators Blimp1, Id2 and Id3...
October 2016: Nature Immunology
https://www.readbyqxmd.com/read/27478306/the-expression-of-t-cell-foxp3-and-t-bet-is-upregulated-in-severe-but-not-euthyroid-hashimoto-s-thyroiditis
#12
Stana Tokić, Mario Štefanić, Ljubica Glavaš-Obrovac, Sonja Jaman, Eva Novosadová, Jana Petrkova, Zdenka Navratilova, Mirjana Suver Stević, Martin Petrek
Hashimoto's thyroiditis (HT) is an organ-specific autoimmune disorder characterized by progressive thyroid failure. Th1 and Treg subset of CD4(+) cells have been implicated in the pathogenesis; however, less is known about their respective roles across the spectrum of HT clinical presentations. To shed more light on CD4(+) subsets role in HT, we investigated the mRNA expression levels of several Th1/Treg-associated transcription factors (T-bet/ETS1, HIF1α/BLIMP1/FOXP3) in peripheral blood T cells of 10 hypothyroid, untreated HT patients, 10 hypothyroid patients undergoing hormone replacement therapy, 12 euthyroid HT subjects, and 11 healthy controls by the qRT-PCR...
2016: Mediators of Inflammation
https://www.readbyqxmd.com/read/27436361/rock2-signaling-is-required-to-induce-a-subset-of-t-follicular-helper-cells-through-opposing-effects-on-stats-in-autoimmune-settings
#13
Jonathan M Weiss, Wei Chen, Melanie S Nyuydzefe, Alissa Trzeciak, Ryan Flynn, James R Tonra, Suzana Marusic, Bruce R Blazar, Samuel D Waksal, Alexandra Zanin-Zhorov
Rho-associated kinase 2 (ROCK2) determines the balance between human T helper 17 (TH17) cells and regulatory T (Treg) cells. We investigated its role in the generation of T follicular helper (TFH) cells, which help to generate antibody-producing B cells under normal and autoimmune conditions. Inhibiting ROCK2 in normal human T cells or peripheral blood mononuclear cells from patients with active systemic lupus erythematosus (SLE) decreased the number and function of TFH cells induced by activation ex vivo. Moreover, inhibition of ROCK2 activity decreased the abundance of the transcriptional regulator Bcl6 (B cell lymphoma 6) and increased that of Blimp1 by reducing the binding of signal transducer and activator of transcription 3 (STAT3) and increasing that of STAT5 to the promoters of the genes Bcl6 and PRDM1, respectively...
July 19, 2016: Science Signaling
https://www.readbyqxmd.com/read/27224915/foxp2-positive-diffuse-large-b-cell-lymphomas-exhibit-a-poor-response-to-r-chop-therapy-and-distinct-biological-signatures
#14
Kah Keng Wong, Duncan M Gascoyne, Elizabeth J Soilleux, Linden Lyne, Hayley Spearman, Giovanna Roncador, Lars M Pedersen, Michael B Møller, Tina M Green, Alison H Banham
FOXP2 shares partially overlapping normal tissue expression and functionality with FOXP1; an established diffuse large B-cell lymphoma (DLBCL) oncogene and marker of poor prognosis. FOXP2 is expressed in the plasma cell malignancy multiple myeloma but has not been studied in DLBCL, where a poor prognosis activated B-cell (ABC)-like subtype display partially blocked plasma cell differentiation. FOXP2 protein expression was detected in ABC-DLBCL cell lines, and in primary DLBCL samples tumoral FOXP2 protein expression was detected in both germinal center B-cell-like (GCB) and non-GCB DLBCL...
August 16, 2016: Oncotarget
https://www.readbyqxmd.com/read/27217539/dynamic-changes-in-id3-and-e-protein-activity-orchestrate-germinal-center-and-plasma-cell-development
#15
Renee Gloury, Dimitra Zotos, Malou Zuidscherwoude, Frederick Masson, Yang Liao, Jhaguaral Hasbold, Lynn M Corcoran, Phil D Hodgkin, Gabrielle T Belz, Wei Shi, Stephen L Nutt, David M Tarlinton, Axel Kallies
The generation of high-affinity antibodies requires germinal center (GC) development and differentiation of long-lived plasma cells in a multilayered process that is tightly controlled by the activity of multiple transcription factors. Here, we reveal a new layer of complexity by demonstrating that dynamic changes in Id3 and E-protein activity govern both GC and plasma cell differentiation. We show that down-regulation of Id3 in B cells is essential for releasing E2A and E2-2, which in a redundant manner are required for antigen-induced B cell differentiation...
May 30, 2016: Journal of Experimental Medicine
https://www.readbyqxmd.com/read/27207558/adrenomedullin-2-improves-early-obesity-induced-adipose-insulin-resistance-by-inhibiting-the-class-ii-mhc-in-adipocytes
#16
Song-Yang Zhang, Ying Lv, Heng Zhang, Song Gao, Ting Wang, Juan Feng, Yuhui Wang, George Liu, Ming-Jiang Xu, Xian Wang, Changtao Jiang
MHC class II (MHCII) antigen presentation in adipocytes was reported to trigger early adipose inflammation and insulin resistance. However, the benefits of MHCII inhibition in adipocytes remain largely unknown. Here, we showed that human plasma polypeptide adrenomedullin 2 (ADM2) levels were negatively correlated with HOMA of insulin resistance in obese human. Adipose-specific human ADM2 transgenic (aADM2-tg) mice were generated. The aADM2-tg mice displayed improvements in high-fat diet-induced early adipose insulin resistance...
August 2016: Diabetes
https://www.readbyqxmd.com/read/27102484/hobit-and-blimp1-instruct-a-universal-transcriptional-program-of-tissue-residency-in-lymphocytes
#17
Laura K Mackay, Martina Minnich, Natasja A M Kragten, Yang Liao, Benjamin Nota, Cyril Seillet, Ali Zaid, Kevin Man, Simon Preston, David Freestone, Asolina Braun, Erica Wynne-Jones, Felix M Behr, Regina Stark, Daniel G Pellicci, Dale I Godfrey, Gabrielle T Belz, Marc Pellegrini, Thomas Gebhardt, Meinrad Busslinger, Wei Shi, Francis R Carbone, René A W van Lier, Axel Kallies, Klaas P J M van Gisbergen
Tissue-resident memory T (Trm) cells permanently localize to portals of pathogen entry, where they provide immediate protection against reinfection. To enforce tissue retention, Trm cells up-regulate CD69 and down-regulate molecules associated with tissue egress; however, a Trm-specific transcriptional regulator has not been identified. Here, we show that the transcription factor Hobit is specifically up-regulated in Trm cells and, together with related Blimp1, mediates the development of Trm cells in skin, gut, liver, and kidney in mice...
April 22, 2016: Science
https://www.readbyqxmd.com/read/26816213/regulation-of-effector-treg-cells-in-murine-lupus
#18
Uma Chandrasekaran, Woelsung Yi, Sanjay Gupta, Chien-Huan Weng, Eugenia Giannopoulou, Yurii Chinenov, Rolf Jessberger, Casey T Weaver, Govind Bhagat, Alessandra B Pernis
OBJECTIVE: Treg cells need to acquire an effector phenotype to function in settings of inflammation. Whether effector Treg cells can limit disease severity in lupus is unknown. Interferon regulatory factor 4 (IRF-4) is an essential controller of effector Treg cells and regulates their ability to express interleukin-10 (IL-10). In non-Treg cells, IRF-4 activity is modulated by interactions with DEF-6 and its homolog switch-associated protein 70 (SWAP-70). Although mice lacking both DEF-6 and SWAP-70 (double-knockout [DKO] mice) develop lupus, they display normal survival, suggesting that in DKO mice, Treg cells can moderate disease development...
June 2016: Arthritis & Rheumatology
https://www.readbyqxmd.com/read/26735971/htlv-1-bzip-factor-impairs-anti-viral-immunity-by-inducing-co-inhibitory-molecule-t-cell-immunoglobulin-and-itim-domain-tigit
#19
Keiko Yasuma, Jun-ichirou Yasunaga, Keiko Takemoto, Kenji Sugata, Yuichi Mitobe, Norihiro Takenouchi, Masanori Nakagawa, Yutaka Suzuki, Masao Matsuoka
Human T-cell leukemia virus type 1 (HTLV-1) infects CD4+ T cells and induces proliferation of infected cells in vivo, which leads to the onset of adult T-cell leukemia (ATL) in some infected individuals. The HTLV-1 bZIP factor (HBZ) gene, which is encoded in the minus strand of HTLV-1, plays critical roles in pathogenesis. In this study, RNA-seq and ChIP-seq analyses using HBZ transduced T cells revealed that HBZ upregulates the expression and promoter acetylation levels of a co-inhibitory molecule, T cell immunoglobulin and ITIM domain (TIGIT), in addition to those of regulatory T cells related genes, Foxp3 and Ccr4...
January 2016: PLoS Pathogens
https://www.readbyqxmd.com/read/26661515/natural-killer-group-2d-and-cd28-receptors-differentially-activate-mammalian-mechanistic-target-of-rapamycin-to-alter-murine-effector-cd8-t-cell-differentiation
#20
Bryan McQueen, Kelsey Trace, Emily Whitman, Taylor Bedsworth, Amorette Barber
Memory CD8+ T cells are an essential component of anti-tumour and anti-viral immunity. Activation of the mammalian/mechanistic target of rapamycin (mTOR) pathway has been implicated in regulating the differentiation of effector and memory T cells. However, the mechanisms that control mTOR activity during immunity to tumours and infections are not well known. Activation of co-stimulatory receptors, including CD28 and natural killer group 2D (NKG2D), activate phosphatidylinositol-3 kinase and subsequently may activate the mTOR pathway in CD8+ T cells...
March 2016: Immunology
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