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https://www.readbyqxmd.com/read/29669243/bach2-an-instrument-of-heterogeneity-for-long-term-protection
#1
Qiutong Huang, Gabrielle T Belz
Generation of functionally diverse effector and memory killer T cells is essential for immediate and long-term protective immunity. Herndler-Brandstetter et al. (2018) report that Bach2 promotes functional plasticity of effector T cells and the transition into the long-term memory compartment by regulating the expression of the inhibitory receptor KLRG1.
April 17, 2018: Immunity
https://www.readbyqxmd.com/read/29625895/klrg1-effector-cd8-t-cells-lose-klrg1-differentiate-into-all-memory-t-cell-lineages-and-convey-enhanced-protective-immunity
#2
Dietmar Herndler-Brandstetter, Harumichi Ishigame, Ryo Shinnakasu, Valerie Plajer, Carmen Stecher, Jun Zhao, Melanie Lietzenmayer, Lina Kroehling, Akiko Takumi, Kohei Kometani, Takeshi Inoue, Yuval Kluger, Susan M Kaech, Tomohiro Kurosaki, Takaharu Okada, Richard A Flavell
Protective immunity against pathogens depends on the efficient generation of functionally diverse effector and memory T lymphocytes. However, whether plasticity during effector-to-memory CD8+ T cell differentiation affects memory lineage specification and functional versatility remains unclear. Using genetic fate mapping analysis of highly cytotoxic KLRG1+ effector CD8+ T cells, we demonstrated that KLRG1+ cells receiving intermediate amounts of activating and inflammatory signals downregulated KLRG1 during the contraction phase in a Bach2-dependent manner and differentiated into all memory T cell linages, including CX3 CR1int peripheral memory cells and tissue-resident memory cells...
March 31, 2018: Immunity
https://www.readbyqxmd.com/read/29570822/type-1-innate-lymphoid-cell-aggravation-of-atherosclerosis-is-mediated-through-tlr4
#3
Chun Wu, Shaolin He, Jie Liu, Boyuan Wang, Jibin Lin, Yanping Duan, Xiaonan Gao, Dazhu Li
ILC populations elaborate a similar cytokine expression pattern with helper T cell subsets Th1, Th2 and Th17. Recent studies indicate that CD25+ILC2 could alleviate atherosclerosis by altering lipid metabolism, whereas the depletion of CD90-expressing ILCs had no influence on atherosclerosis. Thus, these findings raise the question on whether ILC1 cells react on atherosclerosis. Hence, our group attempted to explore the role of ILC1 cells in atherosclerosis. We found that ILC1 cells have a high Th1-like gene expression of T-bet and IFN-γ, which is distinct from ILC2, ILC3, or conventional NK (cNK) cells...
March 23, 2018: Scandinavian Journal of Immunology
https://www.readbyqxmd.com/read/29550509/pinpointing-recurrent-proviral-integration-sites-in-new-models-for-latent-hiv-1-infection
#4
Ulrike C Lange, Julia K Bialek, Thomas Walther, Joachim Hauber
HIV infection is characterized by accumulation of proviral sequences within the human host genome. Integration of viral-derived DNA occurs at preferential loci, suggesting a site-specific crosstalk between viral sequences and human genes. We here describe a genome engineering workflow to generate models for HIV-1 infection that for the first time recapitulate proviral integration at selected genomic loci and provide unique tools to study effects of HIV proviral integration site choice. Using this workflow, we have derived two BACH2-HIV-1 reporter models that mimic largely latent integration in the clinically relevant BACH2 gene locus, which has been associated with recurrent integration and HIV-reservoir maintenance in chronically infected patients...
March 14, 2018: Virus Research
https://www.readbyqxmd.com/read/29540581/bach2-promotes-b-cell-receptor-induced-proliferation-of-b-lymphocytes-and-represses-cyclin-dependent-kinase-inhibitors
#5
Yuichi Miura, Mizuho Morooka, Nicolas Sax, Rahul Roychoudhuri, Ari Itoh-Nakadai, Andrey Brydun, Ryo Funayama, Keiko Nakayama, Susumu Satomi, Mitsuyo Matsumoto, Kazuhiko Igarashi, Akihiko Muto
BTB and CNC homology 2 (Bach2) is a transcriptional repressor that is required for the formation of the germinal center (GC) and reactions, including class switch recombination and somatic hypermutation of Ig genes in B cells, within the GC. Although BCR-induced proliferation is essential for GC reactions, the function of Bach2 in regulating B cell proliferation has not been elucidated. In this study, we demonstrate that Bach2 is required to sustain high levels of B cell proliferation in response to BCR signaling...
March 14, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/29529253/the-critical-role-of-bach2-in-regulating-type-2-chronic-airway-inflammation
#6
Masakatsu Yamashita, Makoto Kuwahara
Although Bach2 (broad complex-tramtrack-bric a brac and Cap'n'collar homology 2) plays an important role in regulating Th2 cell differentiation and type-2 immune responses, the underlying molecular mechanisms remain unclear. Our current studies demonstrate that Bach2 associates with Batf (basic leucine zipper transcription factor ATF-like) family transcription factors and binds to the regulatory regions of the Th2 cytokine gene loci. The Bach2-Batf complex antagonizes the recruitment of the interferon regulatory factor 4 (Irf4)-containing Batf complex to activator protein 1 (AP-1) motifs in the Th2 cytokine gene locus and suppresses Th2 cytokine production and/or Th2 cell differentiation...
February 24, 2018: International Immunology
https://www.readbyqxmd.com/read/29527211/the-footprints-of-poly-autoimmunity-evidence-for-common-biological-factors-involved-in-multiple-sclerosis-and-hashimoto-s-thyroiditis
#7
Simona Perga, Serena Martire, Francesca Montarolo, Ilaria Giordani, Michela Spadaro, Gabriele Bono, Stefania Corvisieri, Ilaria Messuti, Giancarlo Panzica, Fabio Orlandi, Antonio Bertolotto
Autoimmune diseases are a diverse group of chronic disorders and affect a multitude of organs and systems. However, the existence of common pathophysiological mechanisms is hypothesized and reports of shared risk are emerging as well. In this regard, patients with multiple sclerosis (MS) have been shown to have an increased susceptibility to develop chronic autoimmune thyroid diseases, in particular Hashimoto's thyroiditis (HT), suggesting an autoimmune predisposition. However, studies comparing such different pathologies of autoimmune origin are still missing till date...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29511557/bach2-repression-mediates-th17-cell-induced-inflammation-and-associates-with-clinical-features-of-advanced-disease-in-chronic-pancreatitis
#8
M Sasikala, V V Ravikanth, K Murali Manohar, Neha Deshpande, Sandhya Singh, P Pavan Kumar, R Talukdar, Sudip Ghosh, Mohsin Aslam, G V Rao, R Pradeep, D Nageshwar Reddy
Objectives: Altered immune homeostasis and involvement of T cells has been reported in chronic pancreatitis (CP). We evaluated the role of Bach2 (BTB and CNC homology basic leucine zipper transcription factor 2), a key regulator of immune homeostasis in the chronicity of CP. Methods: Expression of Bach2 and T-cell transcription factors, enumeration of BACH2+/CD4+ T-lymphocytes were performed by qRT-PCR and flow cytometry respectively. Bach2 silenced human CD4+ T-lymphocytes were exposed to CP tissue extract to assess T-cell lineage commitment...
March 2018: United European Gastroenterology Journal
https://www.readbyqxmd.com/read/29501569/bach2-regulates-aberrant-activation-of-b-cell-in-systemic-lupus-erythematosus-and-can-be-negatively-regulated-by-bcr-abl-pi3k
#9
Zhengwei Zhu, Chao Yang, Leilei Wen, Lu Liu, Xianbo Zuo, Fusheng Zhou, Jinping Gao, Xiaodong Zheng, Yinjuan Shi, Caihong Zhu, Bo Liang, Xianyong Yin, Wenjun Wang, Hui Cheng, Songke Shen, Xianfa Tang, Huayang Tang, Liangdan Sun, Anping Zhang, Sen Yang, Yong Cui, Xuejun Zhang, Yujun Sheng
OBJECTIVE: This study was aimed to explore the effect of Bach2 on B cells in systemic lupus erythematosus (SLE), as well as the underlying mechanisms. METHODS: Expression of Bach2, phosphorylated-Bach2 (p-Bach2), Akt, p-Akt and BCR-ABL (p210) in B cells isolated from SLE patients and the healthy persons were assessed by Western blot. Immunofluorescence staining was performed to assess the localization of Bach2 in B cells. Enzyme-linked immunosorbent assay (ELISA) was employed to detect IgG produced by B cells...
February 28, 2018: Experimental Cell Research
https://www.readbyqxmd.com/read/29490568/the-relationship-of-circular-rnas-with-ovarian-endometriosis
#10
Xiaoxuan Xu, Shuang-Zheng Jia, Yi Dai, Jun-Ji Zhang, Xiaoyan Li, Jinghua Shi, Jinhua Leng, Jinghe Lang
Circular RNAs (circRNAs) are involved in the pathogenesis of many diseases, although their expression pattern and role in endometriosis remains unknown. Therefore, here, we profiled the expression patterns of circRNAs in ovarian ectopic and paired eutopic endometria as well as constructed a circRNA-miRNA-mRNA network. Circular RNA and messenger RNA (mRNA) expression profiles were assessed by a microarray analysis in 4 patients. Quantitative real-time polymerase chain reaction (qRT-PCR) validation of 8 circRNAs and mRNAs was conducted in another 37 patients...
January 1, 2018: Reproductive Sciences
https://www.readbyqxmd.com/read/29452228/a-bach2-gene-variant-is-associated-with-postoperative-recurrence-of-crohn-s-disease
#11
Michael R Laffin, Richard N Fedorak, Eytan Wine, Bryan Dicken, Karen L Madsen
BACKGROUND: Crohn's disease often requires intestinal resection, which is not considered curative. Repeat surgical intervention is necessary in more than half of patients after their initial operation. Although many genetic loci are implicated in Crohn's disease, few have been associated with post-resection recurrence. STUDY DESIGN: A cohort of patients with Crohn's disease who underwent intestinal resection was analyzed to determine genetic and clinical factors associated with post-resection recurrence...
February 13, 2018: Journal of the American College of Surgeons
https://www.readbyqxmd.com/read/29319368/association-of-increased-eomesodermin-bcl6-and-granzyme-b-expression-with-major-clinical-manifestations-of-hashimoto-s-thyroiditis-an-observational-study
#12
Mario Štefanić, Stana Tokić, Mirjana Suver Stević, Ljubica Glavaš-Obrovac
PURPOSE: Studies of cytotoxic T cells and their respective lineage master regulators have been limited in Hashimoto's thyroiditis (HT). It is unclear whether their transcriptomes are changed in HT patients and how these changes are associated with the thyroid damage, major clinical manifestations, and disease progression. METHODS: We explored the gene expression patterns of selected transcription factors [eomesodermin (EOMES), BACH2, BCL6, TCF1] and cytolytic molecules [granzyme B (GZMB)] in peripheral blood (PB) T cells of 10 healthy controls and 30 HT patients of various subtypes (hypothyroid, untreated HT; L-thyroxine (T4)-treated HT, and spontaneously euthyroid HT) using real-time quantitative PCR...
April 2018: Immunological Investigations
https://www.readbyqxmd.com/read/29230020/snp-co-association-and-network-analyses-identify-e2f3-kdm5a-and-bach2-as-key-regulators-of-the-bovine-milk-fatty-acid-profile
#13
Sara Pegolo, Christos Dadousis, Núria Mach, Yuliaxis Ramayo-Caldas, Marcello Mele, Giuseppe Conte, Stefano Schiavon, Giovanni Bittante, Alessio Cecchinato
The fatty acid (FA) profile has a considerable impact on the nutritional and technological quality of milk and dairy products. The molecular mechanism underlying the regulation of fat metabolism in bovine mammary gland have been not completely elucidated. We conducted genome-wide association studies (GWAS) across 65 milk FAs and fat percentage in 1,152 Brown Swiss cows. In total, we identified 175 significant single nucleotide polymorphism (SNPs) spanning all chromosomes. Pathway analyses revealed that 12:0 was associated with the greatest number of overrepresented categories/pathways (e...
December 11, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29216925/silencing-of-mir-193a-5p-increases-the-chemosensitivity-of-prostate-cancer-cells-to-docetaxel
#14
Zhan Yang, Jin-Suo Chen, Jin-Kun Wen, Hai-Tao Gao, Bin Zheng, Chang-Bao Qu, Kai-Long Liu, Man-Li Zhang, Jun-Fei Gu, Jing-Dong Li, Yan-Ping Zhang, Wei Li, Xiao-Lu Wang, Yong Zhang
BACKGROUND: Docetaxel-based chemotherapy failure in advanced prostate carcinoma has partly been attributed to the resistance of prostate cancer (PC) cells to docetaxel-induced apoptosis. Hence, there is an urgent need to identify mechanisms of docetaxel chemoresistance and to develop new combination therapies. METHODS: miR-193a-5p level was evaluated by qPCR in prostate tissues and cell lines, and its expression in the tissues was also examined by in situ hybridization...
December 8, 2017: Journal of Experimental & Clinical Cancer Research: CR
https://www.readbyqxmd.com/read/29154209/external-signals-regulate-germinal-center-fate-determining-transcription-factors-in-the-a20-lymphoma-cell-line
#15
Juan Feng, Xin Liu, Xingya Ni, Hai Qi
Due to the apoptosis-prone nature of primary germinal center B (GCB) cells, it remains a huge challenge to dissect signals that guide their differentiation towards memory B cells and plasma cells in vitro. Here we show that the murine lymphoma cell line A20 resembles primary GCB cells in expression of GC-specific surface markers and the master transcription factor BCL6 and may serve as a useful system to model certain GCB cell behaviors in vitro. Using these cells, we found that both CD40 and B cell receptor (BCR) signaling are able to drive BCL6 downregulation, which is a prerequisite of post-GC B-cell differentiation...
January 2018: Molecular Immunology
https://www.readbyqxmd.com/read/29129929/il-2-imprints-human-naive-b-cell-fate-towards-plasma-cell-through-erk-elk1-mediated-bach2-repression
#16
Nicolas Hipp, Hannah Symington, Cédric Pastoret, Gersende Caron, Céline Monvoisin, Karin Tarte, Thierry Fest, Céline Delaloy
Plasma cell differentiation is a tightly regulated process that requires appropriate T cell helps to reach the induction threshold. To further understand mechanisms by which T cell inputs regulate B cell fate decision, we investigate the minimal IL-2 stimulation for triggering human plasma cell differentiation in vitro. Here we show that the timed repression of BACH2 through IL-2-mediated ERK/ELK1 signalling pathway directs plasma cell lineage commitment. Enforced BACH2 repression in activated B cells unlocks the plasma cell transcriptional program and induces their differentiation into immunoglobulin M-secreting cells...
November 13, 2017: Nature Communications
https://www.readbyqxmd.com/read/28993481/the-mtor-bach2-cascade-controls-cell-cycle-and-class-switch-recombination-during-b-cell-differentiation
#17
Toru Tamahara, Kyoko Ochiai, Akihiko Muto, Yukinari Kato, Nicolas Sax, Mitsuyo Matsumoto, Takeyoshi Koseki, Kazuhiko Igarashi
The transcription factor Bach2 regulates both acquired and innate immunity at multiple steps, including antibody class switching and regulatory T cell development in activated B and T cells, respectively. However, little is known about the molecular mechanisms of Bach2 regulation in response to signaling of cytokines and antigen. We show here that mammalian target of rapamycin (mTOR) controls Bach2 along B cell differentiation with two distinct mechanisms in pre-B cells. First, mTOR complex 1 (mTORC1) inhibited accumulation of Bach2 protein in nuclei and reduced its stability...
December 15, 2017: Molecular and Cellular Biology
https://www.readbyqxmd.com/read/28924457/bach2-promotes-indolent-clinical-presentation-in-waldenstr%C3%A3-m-macroglobulinemia
#18
Charles Herbaux, Elisabeth Bertrand, Guillemette Marot, Christophe Roumier, Nicolas Poret, Valérie Soenen, Olivier Nibourel, Catherine Roche-Lestienne, Natacha Broucqsault, Sylvie Galiègue-Zouitina, Eileen M Boyle, Guillemette Fouquet, Aline Renneville, Sabine Tricot, Franck Morschhauser, Claude Preudhomme, Bruno Quesnel, Stephanie Poulain, Xavier Leleu
Approximately 30% of the patients who fulfil the criteria of Waldenström's macroglobulinemia (WM) are diagnosed while asymptomatic (indolent), and will not require immediate therapy. Conversely, patients with a disease-related event will be considered for therapy. The physiopathology of these 2 groups remains unclear, and the mechanisms of progression from indolent to symptomatic WM have yet to be fully understood. Seventeen patients diagnosed with WM were included in this study, 8 asymptomatic WM (A-WM) and 9 symptomatic WM (S-WM)...
August 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/28916727/inflammatory-responses-induce-an-identity-crisis-of-alveolar-macrophages-leading-to-pulmonary-alveolar-proteinosis
#19
COMPARATIVE STUDY
Risa Ebina-Shibuya, Mitsuyo Matsumoto, Makoto Kuwahara, Kyoung-Jin Jang, Manabu Sugai, Yoshiaki Ito, Ryo Funayama, Keiko Nakayama, Yuki Sato, Naoto Ishii, Yasunobu Okamura, Kengo Kinoshita, Kohei Kometani, Tomohiro Kurosaki, Akihiko Muto, Masakazu Ichinose, Masakatsu Yamashita, Kazuhiko Igarashi
Pulmonary alveolar proteinosis (PAP) is a severe respiratory disease characterized by dyspnea caused by accumulation of surfactant protein. Dysfunction of alveolar macrophages (AMs), which regulate the homeostasis of surfactant protein, leads to the development of PAP; for example, in mice lacking BTB and CNC homology 2 (Bach2). However, how Bach2 helps prevent PAP is unknown, and the cell-specific effects of Bach2 are undefined. Using mice lacking Bach2 in specific cell types, we found that the PAP phenotype of Bach2 -deficient mice is due to Bach2 deficiency in more than two types of immune cells...
November 3, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28887441/hiv-1-mediated-insertional-activation-of-stat5b-and-bach2-trigger-viral-reservoir-in-t-regulatory-cells
#20
Daniela Cesana, Francesca R Santoni de Sio, Laura Rudilosso, Pierangela Gallina, Andrea Calabria, Stefano Beretta, Ivan Merelli, Elena Bruzzesi, Laura Passerini, Silvia Nozza, Elisa Vicenzi, Guido Poli, Silvia Gregori, Giuseppe Tambussi, Eugenio Montini
HIV-1 insertions targeting BACH2 or MLK2 are enriched and persist for decades in hematopoietic cells from patients under combination antiretroviral therapy. However, it is unclear how these insertions provide such selective advantage to infected cell clones. Here, we show that in 30/87 (34%) patients under combination antiretroviral therapy, BACH2, and STAT5B are activated by insertions triggering the formation of mRNAs that contain viral sequences fused by splicing to their first protein-coding exon. These chimeric mRNAs, predicted to express full-length proteins, are enriched in T regulatory and T central memory cells, but not in other T lymphocyte subsets or monocytes...
September 8, 2017: Nature Communications
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