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Blimp1 t cell

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https://www.readbyqxmd.com/read/29141218/reciprocal-expression-of-il-35-and-il-10-defines-two-distinct-effector-treg-subsets-that-are-required-for-maintenance-of-immune-tolerance
#1
Xundong Wei, Jianhua Zhang, Qianchong Gu, Man Huang, Wei Zhang, Jie Guo, Xuyu Zhou
Regulatory T cells (Tregs) can exert their functions through multiple suppressive mechanisms; however, it is unclear how Tregs exactly employ these mechanisms. In this study, we found that interleukin-35 (IL-35)-producing Tregs were a distinct effector population from the IL-10-producing subset. We also revealed that these two subsets of effector Tregs have different transcription factor dependency. Terminal differentiation regulator Blimp1 was only critical for IL-10 production, but not for IL-35; Foxp3 was essential for IL-35 but dispensable for IL-10 production...
November 14, 2017: Cell Reports
https://www.readbyqxmd.com/read/28935958/differential-regulation-of-effector-and-regulatory-t-cell-function-by-blimp1
#2
Rashmi Bankoti, Chihiro Ogawa, Truc Nguyen, Lena Emadi, Michael Couse, Soofia Salehi, Xuemo Fan, Deepti Dhall, Yizhou Wang, Jordan Brown, Vincent Funari, Jie Tang, Gislâine A Martins
The transcriptional regulator Blimp1 plays crucial roles in controlling terminal differentiation in several lineages. In T cells, Blimp1 is expressed in both effector (Teff) and regulatory (Treg) cells, and mice with T cell-specific deletion of Blimp1 (Blimp1CKO mice) spontaneously develop severe intestinal inflammation, indicating a crucial role for Blimp1 in T cell homeostasis regulation. Blimp1 has been shown to function as a direct activator of the Il10 gene and although its requirement for IL10 expression has been demonstrated in both Treg and Teff cells under inflammatory conditions, the intrinsic requirement of Blimp1 for homeostatic maintenance of these T cell subsets had not been investigated...
September 21, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28875978/il4-and-il21-cooperate-to-induce-the-high-bcl6-protein-level-required-for-germinal-center-formation
#3
Stéphane Chevrier, Tobias Kratina, Dianne Emslie, David M Tarlinton, Lynn M Corcoran
Bcl6 is a transcriptional repressor and critical mediator of the germinal center reaction during a T cell dependent antibody response, where it enables somatic hypermutation of immunoglobulin genes and inhibits terminal differentiation via repression of Blimp1. It can also contribute to the development of diffuse large B cell lymphoma when expressed inappropriately. Bcl6 regulation is mediated both at the transcriptional and post-transcriptional levels, and in particular a strong signal through the B cell receptor causes rapid proteasomal degradation of Bcl6...
September 6, 2017: Immunology and Cell Biology
https://www.readbyqxmd.com/read/28851699/an-aberrant-notch2-bcr-signaling-axis-in-b-cells-from-patients-with-chronic-gvhd
#4
Jonathan C Poe, Wei Jia, Hsuan Su, Sarah Anand, Jeremy J Rose, Prasanthi V Tata, Amy N Suthers, Corbin D Jones, Pei Fen Kuan, Benjamin G Vincent, Jonathan S Serody, Mitchell E Horwitz, Vincent T Ho, Steven Z Pavletic, Frances T Hakim, Kouros Owzar, Dadong Zhang, Bruce R Blazar, Christian W Siebel, Nelson J Chao, Ivan Maillard, Stefanie Sarantopoulos
B Cell Receptor (BCR)-activated B cells contribute to pathogenesis in chronic graft-versus-host disease (cGVHD), a condition manifested by both B cell autoreactivity and immune deficiency. We hypothesized that constitutive BCR activation precluded functional B cell maturation in cGVHD. To address this, we examined BCR-NOTCH2 synergy, since Notch has been shown to increase BCR responsiveness in normal mouse B cells. We conducted ex vivo activation and signaling assays of 30 primary samples from HCT patients with and without cGVHD...
August 29, 2017: Blood
https://www.readbyqxmd.com/read/28833081/transcriptional-repressor-blimp1-regulates-follicular-regulatory-t-cell-homeostasis-and-function
#5
Guang Yang, Xiaosu Yang, Junmei Zhang, Guancheng Li, Dandan Zheng, Anjiao Peng, Jue Hu, Liqun Xu, Baifeng Yang, Huan Yang, Wenbin Zhou, Erdem Tuzun, Jing Li
The B-lymphocyte-induced maturation protein 1 (Blimp1) regulates T-cell homeostasis and function. Loss of Blimp1 could double the proportion of follicular regulatory T (Tfr) cells. However, the effects that Blimp1 may have on the function of Tfr cells remain unknown. Here we document the function for Blimp1 in Tfr cells in vitro and in vivo. Data presented in this study demonstrate that Tfr cells indirectly inhibit the activation and differentiation of B cells by negatively regulating follicular helper T cells, so lowering the secretion of antibody...
August 20, 2017: Immunology
https://www.readbyqxmd.com/read/28768724/pd-l2-regulates-b-1-cell-antibody-production-against-phosphorylcholine-through-an-il-5-dependent-mechanism
#6
Jerome T McKay, Marcela A Haro, Christina A Daly, Rama D Yammani, Bing Pang, W Edward Swords, Karen M Haas
B-1 cells produce natural Abs which provide an integral first line of defense against pathogens while also performing important homeostatic housekeeping functions. In this study, we demonstrate that programmed cell death 1 ligand 2 (PD-L2) regulates the production of natural Abs against phosphorylcholine (PC). Naive PD-L2-deficient (PD-L2(-/-)) mice produced significantly more PC-reactive IgM and IgA. This afforded PD-L2(-/-) mice with selectively enhanced protection against PC-expressing nontypeable Haemophilus influenzae, but not PC-negative nontypeable Haemophilus influenzae, relative to wild-type mice...
September 15, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28758191/interleukin-27-signalling-induces-stem-cell-antigen-1-expression-in-t-lymphocytes-in%C3%A2-vivo
#7
Zhihao Liu, Lisha Wu, Jing Zhu, Xiaotong Zhu, Jianmin Zhu, Jin-Qing Liu, Jianchao Zhang, Jonathan P Davis, Sanjay Varikuti, Abhay R Satoskar, Jie Zhou, Ming-Song Li, Xue-Feng Bai
Stem cell antigen-1 (Sca-1/Ly6A/E) is a cell surface glycoprotein that is often used as a biomarker for stem cells and cell stemness. However, it is not clear what factors can directly induce the expression of Sca-1/Ly6A/E in T lymphocytes in vivo, and if induction of Sca-1 is associated with T cell stemness. In this study, we show that interleukin-27 (IL-27), a member of the IL-12 family of cytokines, directly induces Sca-1 expression in T cells in vivo. We found that mice-deficient for IL-27 (either P28 or EBI3) or its signalling (IL-27Rα) had profound reduction of Sca-1 expression in naive (CD62L(+)  CD44(-) ), memory (CD62L(+)  CD44(+) ) and effector (CD62L(-)  CD44(+) ) T cells...
December 2017: Immunology
https://www.readbyqxmd.com/read/28723546/local-modulation-of-antigen-presenting-cell-development-after-resolution-of-pneumonia-induces-long-term-susceptibility-to-secondary-infections
#8
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
#9
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...
August 15, 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
#10
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...
August 1, 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
#11
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
#12
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
#13
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...
July 1, 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
#14
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
#15
REVIEW
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
#16
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
#17
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
#18
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
#19
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
#20
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
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