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JOURNAL ARTICLE
Enrica Marchi, Jeffrey W Craig, Matko Kalac
Rare subtypes of peripheral T-cell lymphoma (PTCL) including enteropathy-associated T-cell lymphoma (EATL), monomorphic epitheliotropic intestinal T-cell lymphoma (MEITL), subcutaneous panniculitis-like T-cell lymphoma (SPTCL) and hepatosplenic T-cell lymphoma (HSTCL) are underrepresented in most registry and clinical studies. Most of the literature is obtained from small case series, single-institution retrospective studies and subgroup analyses of the largest studies with few recent and ongoing exceptions...
April 24, 2024: Blood
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JOURNAL ARTICLE
Thiruvaimozhi Abimannan, Velayoudame Parthibane, Si-Hung Le, Nagampalli Vijaykrishna, Stephen D Fox, Baktiar Karim, Govind Kunduri, Daniel Blankenberg, Thorkell Andresson, Takeshi Bamba, Usha Acharya, Jairaj K Acharya
T helper 17 (TH 17) cells are implicated in autoimmune diseases, and several metabolic processes are shown to be important for their development and function. In this study, we report an essential role for sphingolipids synthesized through the de novo pathway in TH 17 cell development. Deficiency of SPTLC1, a major subunit of serine palmitoyl transferase enzyme complex that catalyzes the first and rate-limiting step of de novo sphingolipid synthesis, impaired glycolysis in differentiating TH 17 cells by increasing intracellular reactive oxygen species (ROS) through enhancement of nicotinamide adenine dinucleotide phosphate oxidase 2 activity...
April 26, 2024: Science Advances
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JOURNAL ARTICLE
Ka Lung Cheung, Li Zhao, Rajal Sharma, Anurupa Abhijit Ghosh, Michael Appiah, Yifei Sun, Anbalagan Jaganathan, Yuan Hu, Alannah LeJeune, Feihong Xu, Xinye Han, Xueting Wang, Fan Zhang, Chunyan Ren, Martin J Walsh, Huabao Xiong, Alexander Tsankov, Ming-Ming Zhou
Class II histone deacetylases (HDACs) are important in regulation of gene transcription during T cell development. However, our understanding of their cell-specific functions is limited. In this study, we reveal that class IIa Hdac4 and Hdac7 (Hdac4/7) are selectively induced in transcription, guiding the lineage-specific differentiation of mouse T-helper 17 (Th17) cells from naive CD4+ T cells. Importantly, Hdac4/7 are functionally dispensable in other Th subtypes. Mechanistically, Hdac4 interacts with the transcription factor (TF) JunB, facilitating the transcriptional activation of Th17 signature genes such as Il17a/f ...
April 30, 2024: Proceedings of the National Academy of Sciences of the United States of America
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JOURNAL ARTICLE
Ian Bell, Haider Khan, Nathan Stutt, Matthew Horn, Teesha Hydzik, Whitney Lum, Victoria Rea, Emma Clapham, Lisa Hoeg, Terence J Van Raay
Wnt signaling is a crucial developmental pathway involved in early development as well as stem cell maintenance in adults and its misregulation leads to numerous diseases. Thus, understanding the regulation of this pathway becomes vitally important. Axin2 and Nkd1 are widely utilized negative feedback regulators in Wnt signaling where Axin2 functions to destabilize cytoplasmic β-catenin, and Nkd1 functions to inhibit the nuclear localization of β-catenin. Here, we set out to further understand how Axin2 and Nkd1 regulate Wnt signaling by creating axin2gh1/gh1 , nkd1gh2/gh2 single mutants and axin2gh1/gh1 ;nkd1gh2 /gh2 double mutant zebrafish using sgRNA/Cas9...
April 24, 2024: Molecular Biology of the Cell
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JOURNAL ARTICLE
Harini Bagavant, Justyna Durslewicz, Marcelina Pyclik, Magdalena Makuch, Joanna A Papinska, Umesh S Deshmukh
Sjögren's disease (SjD), characterized by circulating autoantibodies and exocrine gland inflammation, is typically diagnosed in women over 50 years of age. However, the contribution of age to SjD pathogenesis is unclear. C57BL/6 female mice at different ages were studied to investigate how aging influences the dynamics of salivary gland inflammation. Salivary glands were characterized for immune cell infiltration, inflammatory gene expression, and saliva production. At 8 months, gene expression of several chemokines involved in immune cell trafficking was significantly elevated...
April 24, 2024: GeroScience
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JOURNAL ARTICLE
Anastasia Geladaris, Sebastian Torke, Darius Saberi, Yasemin B Alankus, Frank Streit, Sabrina Zechel, Christine Stadelmann-Nessler, Andreas Fischer, Ursula Boschert, Darius Häusler, Martin S Weber
In multiple sclerosis (MS), persisting disability can occur independent of relapse activity or development of new central nervous system (CNS) inflammatory lesions, termed chronic progression. This process occurs early and it is mostly driven by cells within the CNS. One promising strategy to control progression of MS is the inhibition of the enzyme Bruton's tyrosine kinase (BTK), which is centrally involved in the activation of both B cells and myeloid cells, such as macrophages and microglia. The benefit of BTK inhibition by evobrutinib was shown as we observed reduced pro-inflammatory activation of microglia when treating chronic experimental autoimmune encephalomyelitis (EAE) or following the adoptive transfer of activated T cells...
April 24, 2024: Acta Neuropathologica
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JOURNAL ARTICLE
Ameera Hasan, Jose J Macias, Brashé Wood, Megan Malone-Perez, Gilseung Park, Clay A Foster, J Kimble Frazer
The thymus is the site of T lymphocyte development and T cell education to recognize foreign, but not self, Ags. B cells also reside and develop in the thymus, although their functions are less clear. During "thymic involution," a process of lymphoid atrophy and adipose replacement linked to sexual maturation, thymocytes decline. However, thymic B cells decrease far less than T cells, such that B cells comprise ∼1% of human neonatal thymocytes but up to ∼10% in adults. All jawed vertebrates possess a thymus, and we and others have shown zebrafish (Danio rerio) also have thymic B cells...
April 24, 2024: Journal of Immunology
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JOURNAL ARTICLE
Junze Liu, Yuan Li, Dan Shen, Xiaoqing Li, Kai Wang, Kentaro Nagaoka, Chunmei Li
UNLABELLED: The gut microbiota of poultry is influenced by a variety of factors, including feed, drinking water, airborne dust, and footpads, among others. Gut microbiota can affect the immune reaction and inflammation in the lungs. To investigate the effect of gut microbiota variation on lung inflammation induced by PM2.5 (fine particulate matter) in broilers, 36 Arbor Acres (AA) broilers were randomly assigned to three groups: control group (CON), PM2.5 exposure group (PM), and PM2...
April 24, 2024: Applied and Environmental Microbiology
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JOURNAL ARTICLE
Rajan M Thomas, Matthew C Pahl, Liqing Wang, Struan F A Grant, Wayne W Hancock, Andrew D Wells
Ikaros is a transcriptional factor required for conventional T cell development, differentiation, and anergy. While the related factors Helios and Eos have defined roles in regulatory T cells (Treg), a role for Ikaros has not been established. To determine the function of Ikaros in the Treg lineage, we generated mice with Treg-specific deletion of the Ikaros gene ( Ikzf1 ). We find that Ikaros cooperates with Foxp3 to establish a major portion of the Treg epigenome and transcriptome. Ikaros-deficient Treg exhibit Th1-like gene expression with abnormal production of IL-2, IFNg, TNFa, and factors involved in Wnt and Notch signaling...
April 24, 2024: ELife
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JOURNAL ARTICLE
Zaigham Abbas Rizvi, Srikanth Sadhu, Jyotsna Dandotiya, Puja Sharma, Akshay Binayke, Virendra Singh, Vinayaka Das, Ritika Khatri, Rajesh Kumar, Sweety Samal, Manjula Kalia, Amit Awasthi
Pathogenic infections cause thymic atrophy, perturb thymic T-cell development, and alter immunological response. Previous studies reported dysregulated T-cell function and lymphopenia in coronavirus disease-19 (COVID-19). However, immunopathological changes in the thymus associated with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection have not been elucidated. Here, we report that SARS-CoV-2 infects thymocytes, and induces CD4+ CD8+ (double positive; DP) T-cell apoptosis leading to thymic atrophy and loss of peripheral TCR repertoire in K18-hACE2 transgenic mice...
April 24, 2024: European Journal of Immunology
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JOURNAL ARTICLE
Crystal Y Li, Salih Salihoglu, Francisco J Civantos, Jaylou M Velez Torres
NUT carcinoma (NC) is a highly aggressive, poorly differentiated carcinoma that harbors a t(15:19) translocation, leading to the fusion of the NUTM1 gene. While the upper aerodigestive tract along the midline (head, neck, thorax, and mediastinum) is commonly reported as the primary site of NC, subsequent cases have emerged in diverse locations. Achieving a definitive diagnosis based solely on morphology is challenging; however, it can be achieved using immunohistochemistry (IHC) specific to the NUT antibody or by demonstrating the characteristic BRD4::NUTM1 fusion...
April 24, 2024: Diagnostic Cytopathology
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JOURNAL ARTICLE
Dan Tan, Ning Kang, Yuanfei Zhu, Jia Hou, Hanqing Wang, Huijun Xu, Cheng Zu, Zixiang Gao, Mu Liu, Nannan Liu, Qiang Deng, Hongzhou Lu, Jing Liu, Youhua Xie
Vaccines play essential roles in the fight against the COVID-19 pandemic. The development and assessment of COVID-19 vaccines have generally focused on the induction and boosting of neutralizing antibodies targeting the SARS-CoV-2 spike (S) protein. Due to rapid and continuous variation in the S protein, such vaccines need to be regularly updated to match newly emerged dominant variants. T-cell vaccines that target MHC I- or II-restricted epitopes in both structural and non-structural viral proteins have the potential to induce broadly cross-protective and long-lasting responses...
April 24, 2024: Acta Biochimica et Biophysica Sinica
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JOURNAL ARTICLE
Jiaxin Qiu, Haibo Wu, Qin Xie, Yuxiao Zhou, Yining Gao, Junbo Liu, Xueyi Jiang, Lun Suo, Yanping Kuang
Introduction: Mitochondrial diseases caused by mtDNA have no effective cures. Recently developed DddA-derived cytosine base editors (DdCBEs) have potential therapeutic implications in rescuing the mtDNA mutations. However, the performance of DdCBEs relies on designing different targets or improving combinations of split-DddA halves and orientations, lacking knowledge of predicting the results before its application. Methods: A series of DdCBE pairs for wide ranges of aC or tC targets was constructed, and transfected into Neuro-2a cells...
2024: Frontiers in Bioengineering and Biotechnology
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JOURNAL ARTICLE
Valerine C Chunda, Fanny Fri Fombad, Chi Anizette Kien, Rene Ebai, Frederick Esofi, Anna Ning Ntuh, Emmanuel Ouam, Narcisse Victor Tchamatchoua Gandjui, Relindis Ekanya, Franck Nietcho, Lucy Cho Nchang, Chefor Magha, Abdel Jelil Njouendou, Peter Enyong, Achim Hoerauf, Samuel Wanji, Manuel Ritter
INTRODUCTION: Mouse models of human filarial infections are not only urgently needed to investigate the biology of the nematodes and their modulation of the host's immunity, but will also provide a platform to screen and test novel anti-filarial drugs. Recently, murine Loa loa infection models have been stablished using immunocompromised mouse strains, whereas murine Mansonella perstans infections have not been implemented until now. METHODS: Therefore, we aim to establish experimental M...
April 15, 2024: Frontiers in tropical diseases
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JOURNAL ARTICLE
Tiffany Hood, Fern Slingsby, Viktor Sandner, Winfried Geis, Timo Schmidberger, Nicola Bevan, Quentin Vicard, Julia Hengst, Pierre Springuel, Noushin Dianat, Qasim A Rafiq
Ex vivo genetically-modified cellular immunotherapies, such as chimeric antigen receptor T cell (CAR-T) therapies, have generated significant clinical and commercial outcomes due to their unparalleled response rates against relapsed and refractory blood cancers. However, the development and scalable manufacture of these novel therapies remains challenging and further process understanding and optimisation is required to improve product quality and yield. In this study, we employ a quality-by-design (QbD) approach to systematically investigate the impact of critical process parameters (CPPs) during the expansion step on the critical quality attributes (CQAs) of CAR-T cells...
2024: Frontiers in Immunology
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Youngbin Cho, Matthew Laird, Teddi Bishop, Ruxuan Li, Elisa Ruffo, Jason Lohmueller, Ioannis K Zervantonakis
The success of chimeric antigen receptor (CAR) T cells in blood cancers has intensified efforts to develop CAR T therapies for solid cancers. In the solid tumor microenvironment, CAR T cell trafficking and suppression of cytotoxic killing represent limiting factors for therapeutic efficacy. Here, we present a microwell platform to study CAR T cell interactions with 3D tumor spheroids and determine predictors of anti-tumor CAR T cell function. To precisely control antigen sensing by CAR T cells, we utilized a switchable adaptor CAR system, that instead of directly binding to an antigen of interest, covalently attaches to co-administered antibody adaptors that mediate tumor antigen recognition...
March 15, 2024: bioRxiv
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JOURNAL ARTICLE
Linhua Huang, Rui Gao, Lidi Nan, Jingyao Qi, Siyu Yang, Shuai Shao, Jiajun Xie, Mingzhu Pan, Tianquan Qiu, Juan Zhang
Immunocytokines are a promising immunotherapeutic approach in cancer therapy. Anti-VEGFR2-interferon α (IFNα) suppressed colorectal cancer (CRC) growth and enhanced CD8+ T-cell infiltration in the tumor microenvironment, exhibiting great clinical translational potential. However, the mechanism of how the anti-VEGFR2-IFNα recruits T cells has not been elucidated. Here, we demonstrated that anti-VEGFR2-IFNα suppressed CRC metastasis and enhanced CD8+ T-cell infiltration. RNA sequencing revealed a transcriptional activation of CCL5 in metastatic CRC cells, which was correlated with T-cell infiltration...
April 24, 2024: Journal of Immunotherapy
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JOURNAL ARTICLE
Kang Huang, Xuehan Huang, Chengbing Zeng, Siyan Wang, Yizhou Zhan, Qingxin Cai, Guobo Peng, Zhining Yang, Li Zhou, Jianzhou Chen, Chuangzhen Chen
BACKGROUND: Our previous study suggests that tumor CD8+ T cells and macrophages (defined as CD68+ cells) infiltration underwent dynamic and heterogeneous changes during concurrent chemoradiotherapy (CCRT) in cervical cancer patients, which correlated with their short-term tumor response. This study aims to develop a CT image-based radiomics signature for such dynamic changes. METHODS: Thirty cervical squamous cell carcinoma patients, who were treated with CCRT followed by brachytherapy, were included in this study...
April 23, 2024: Cancer Imaging: the Official Publication of the International Cancer Imaging Society
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JOURNAL ARTICLE
Christopher J Buswinka, David B Rosenberg, Rubina G Simikyan, Richard T Osgood, Katharine Fernandez, Hidetomi Nitta, Yushi Hayashi, Leslie W Liberman, Emily Nguyen, Erdem Yildiz, Jinkyung Kim, Amandine Jarysta, Justine Renauld, Ella Wesson, Haobing Wang, Punam Thapa, Pierrick Bordiga, Noah McMurtry, Juan Llamas, Siân R Kitcher, Ana I López-Porras, Runjia Cui, Ghazaleh Behnammanesh, Jonathan E Bird, Angela Ballesteros, A Catalina Vélez-Ortega, Albert S B Edge, Michael R Deans, Ksenia Gnedeva, Brikha R Shrestha, Uri Manor, Bo Zhao, Anthony J Ricci, Basile Tarchini, Martín L Basch, Ruben Stepanyan, Lukas D Landegger, Mark A Rutherford, M Charles Liberman, Bradley J Walters, Corné J Kros, Guy P Richardson, Lisa L Cunningham, Artur A Indzhykulian
Our sense of hearing is mediated by cochlear hair cells, of which there are two types organized in one row of inner hair cells and three rows of outer hair cells. Each cochlea contains 5-15 thousand terminally differentiated hair cells, and their survival is essential for hearing as they do not regenerate after insult. It is often desirable in hearing research to quantify the number of hair cells within cochlear samples, in both pathological conditions, and in response to treatment. Machine learning can be used to automate the quantification process but requires a vast and diverse dataset for effective training...
April 23, 2024: Scientific Data
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JOURNAL ARTICLE
W S Yiu, T S M Chu, Y Meng, F-M Spring Kong
AIMS: ERCC1 rs11615 and ERCC2 rs238406 single nuclear polymorphism (SNPs) are known for their association with treatment outcome, likely related to radiosensitivity of both tumor and normal tissue in patients with non-small-cell lung cancer. This study aimed to review the effect of 1) these ERCC1/2 SNPs and 2) other SNPs of DNA repair genes on radiation pneumonitis (RP) in patients with lung cancer. MATERIALS AND METHODS: SNPs of our interest included ERCC1 rs11615 and ERCC2 rs238406 and other genes of DNA repair pathways that are functional and biologically active...
March 24, 2024: Clinical Oncology: a Journal of the Royal College of Radiologists
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