Article
Genetics & Heredity
Blagoje Soskic, Eddie Cano-Gamez, Deborah J. Smyth, Kirsty Ambridge, Ziying Ke, Julie C. Matte, Lara Bossini-Castillo, Joanna Kaplanis, Lucia Ramirez-Navarro, Anna Lorenc, Nikolina Nakic, Jorge Esparza-Gordillo, Wendy Rowan, David Wille, David F. Tough, Paola G. Bronson, Gosia Trynka
Summary: Single-cell RNA sequencing reveals dynamic regulation of gene expression during T cell activation, which may provide insights into the genetic susceptibility to immune diseases.
Article
Immunology
Michael C. McGee, Tianyi Zhang, Nicholas Magazine, Rezwanul Islam, Mariano Carossino, Weishan Huang
Summary: This study characterized the development and molecular features of tissue resident regulatory T cells (TR-Treg cells) during repetitive heterosubtypic influenza infections. The results showed that lung tissue resident Treg cells accumulated and expressed high levels of co-inhibitory and co-stimulatory receptors after primary and secondary infections. The PD-1 and ICOS signaling pathways counter-regulated the expansion and IL-10 production of TR-Treg cells during secondary influenza infection. Furthermore, the virus-specific TR-Treg cell response displayed distinct kinetics compared to conventional CD4(+) tissue resident memory T cells during secondary flu infection.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Allergy
Ni Wang, Susanne Brix, Jeppe M. Larsen, Anna H. Thysen, Morten A. Rasmussen, Christopher T. Workman, Jakob Stokholm, Klaus Bonnelykke, Hans Bisgaard, Bo L. Chawes
Summary: The effects of two variants at the 17q21 locus on childhood asthma risk were mediated by immune parameters induced in response to intracellular bacterial DNA (CpG) and double-stranded viral RNA (poly(I:C)), highlighting a potential link between genetic risk variants and immune responses in childhood asthma development.
CLINICAL AND EXPERIMENTAL ALLERGY
(2021)
Article
Respiratory System
Hanna M. Knihtila, Rachel S. Kelly, Nicklas Brustad, Mengna Huang, Priyadarshini Kachroo, Bo L. Chawes, Jakob Stokholm, Klaus Bonnelykke, Casper-Emil T. Pedersen, Hans Bisgaard, Augusto A. Litonjua, Jessica A. Lasky-Su, Scott T. Weiss
Summary: Prenatal vitamin D-3 supplementation has a protective effect against offspring asthma/recurring wheeze, which is influenced by maternal 17q21 genotype variation. Offspring of mothers with low-risk genotype show significant reduction in risk with high-dose vitamin D-3 supplementation, while no difference was observed in offspring of mothers with high-risk genotype.
EUROPEAN RESPIRATORY JOURNAL
(2021)
Article
Multidisciplinary Sciences
Sierra M. Collins, Katherine A. Alexander, Stefan Lundh, Alexander J. Dimitri, Zhen Zhang, Charly R. Good, Joseph A. Fraietta, Shelley L. Berger
Summary: Chimeric antigen receptor (CAR) T cell therapy is hindered by T cell exhaustion (T-EX), but loss of TET2 gene enhances central memory T cell differentiation and antitumor efficacy. TET2 deficiency increases chromatin accessibility and expression of TOX2, an exhaustion regulator. Knockdown of TOX increases T-CM percentage, while knockdown of TOX2 decreases T-CM percentage and proliferation. TOX2 binds to promoters of T-CM genes, suggesting its role in CAR T cell therapy via modulated TOX2 expression.
Article
Biochemistry & Molecular Biology
Koji Kitamura, Hidefumi Suzuki, Ryota Abe, Hidenori Inohara, Yasufumi Kaneda, Hidehisa Takahashi, Keisuke Nimura
Summary: This study reveals that the splicing factor SF3B2 plays a role in regulating transcription and RNA stability in head and neck squamous cell carcinoma. High SF3B2 expression is associated with poor prognosis and accelerated tumor growth. SF3B2 has a dual function in both transcription and RNA stability.
CELL AND BIOSCIENCE
(2022)
Article
Respiratory System
Allison J. Burbank, Stephen A. Schworer, Amika Sood, Martha Almond, Kelly Chason, Nathan Bean, Haibo Zhou, Michelle L. Hernandez
Summary: This study found a positive association between airway IL-1 beta concentration and biomarkers of T2 inflammation in acute allergen-induced asthma exacerbation in humans. The results suggest that IL-1 beta plays a role in the pathophysiology of allergic asthma and further study on its role in human asthma is warranted.
RESPIRATORY RESEARCH
(2021)
Article
Medicine, Research & Experimental
Sana Siddiqui, Kristina Johansson, Alex Joo, Luke R. Bonser, Kyung Duk Koh, Olivier Le Tonqueze, Samaneh Bolourchi, Rodriel A. Bautista, Lorna Zlock, Theodore L. Roth, Alexander Marson, Nirav R. Bhakta, K. Mark Ansel, Walter E. Finkbeiner, David J. Erle, Prescott G. Woodruff
Summary: The study identifies miR-141 as a key regulator of pathological airway mucus production induced by IL-13, with disruption leading to decreased goblet cell frequency and reduced mucus secretion. This miRNA may offer a novel therapeutic target for airway diseases.
Article
Allergy
Sibtain Afzal, Khushnooda Ramzan, Sajjad Ullah, Arshad Jamal, Sulman Basit, Khaled M. AlKattan, Ahmed Bilal Waqar
Summary: This study analyzed the frequencies of four SNPs in the Pashtun population of Pakistan and found that three of them are significantly associated with asthma susceptibility in females.
Article
Allergy
Aurora Holgado, Zhuangzhuang Liu, Aigerim Aidarova, Christina Mueller, Mira Haegman, Yasmine Driege, Marja Kreike, Charlotte L. Scott, Inna S. Afonina, Rudi Beyaert
Summary: IL-33 plays a crucial role in allergic diseases, and A20 is involved in regulating IL-33 signaling. In the absence of A20 in macrophages, IL-33-induced lung immune responses are altered, with reduced type 2 immune response and increased production of IFN-gamma. This study reveals a novel role for A20 in regulating IL-33-induced STAT1 signaling in macrophages.
JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY
(2023)
Article
Allergy
Mehdi Benamar, Hani Harb, Qian Chen, Muyun Wang, Tsz Man Fion Chan, Jason Fong, Wanda Phipatanakul, Amparito Cunningham, Deniz Ertem, Carter R. Petty, Amirhosein J. Mousavi, Constantinos Sioutas, Elena Crestani, Talal A. Chatila
Summary: The interaction between IL-4R alpha R576 and Notch4 promotes asthmatic inflammation. Asthmatics carrying the IL4R(R576) allele have increased Notch4 expression on their T-reg cells. Mice harboring the Il4ra(R576) allele exhibit increased Notch4-dependent allergic airway inflammation.
Article
Medicine, Research & Experimental
Stephanie Kim, Rami Khoriaty, Lu Li, Madison McClune, Theodosia A. Kalfa, Julia Wu, Daniel Peltier, Hideaki Fujiwara, Yaping Sun, Katherine Oravecz-Wilson, Richard A. King, David Ginsburg, Pavan Reddy
Summary: The activation of T cells leads to increased trafficking via the ER-to-Golgi pathway, which is crucial for the regulation of T cell secretome. Deficiency of SEC23B may impair T cell functions, while increased levels of SEC23A in CDAII patients' T cells contribute to maintaining their functions.
JOURNAL OF CLINICAL INVESTIGATION
(2021)
Article
Biology
Yuzhou Xue, Minghao Luo, Xiankang Hu, Xiang Li, Jian Shen, Wenyan Zhu, Longxiang Huang, Yu Hu, Yongzheng Guo, Lin Liu, Lingbang Wang, Suxin Luo
Summary: It has been discovered that during the progression of atherosclerosis, lipid deposits cause functional changes in macrophage-like vascular smooth muscle cells (VSMCs), which are primarily regulated by the IL-1 beta/STAT3 signaling pathway.
COMMUNICATIONS BIOLOGY
(2022)
Article
Medicine, Research & Experimental
Huanyi Zhao, Fang Dong, Yuhui Li, Xiaojie Ren, Zhengyuan Xia, Yong Wang, Wuhua Ma
Summary: Acupuncture reduces airway inflammation and AHR in asthma by inhibiting ATG5-mediated autophagy to regulate endoplasmic reticulum stress and CD4(+) T lymphocyte differentiation.
BIOMEDICINE & PHARMACOTHERAPY
(2021)
Article
Pharmacology & Pharmacy
Haixia Wang, Yuanmin Jia, Junlian Gu, Ou Chen, Shouwei Yue
Summary: This study identified ferroptosis-related genes associated with asthma and their regulation of the immune microenvironment, providing potential therapeutic targets. The results could be useful for immunotherapy and prognostic markers in asthma.
FRONTIERS IN PHARMACOLOGY
(2023)
Article
Genetics & Heredity
Vivek Chandra, Sourya Bhattacharyya, Benjamin J. Schmiedel, Ariel Madrigal, Cristian Gonzalez-Colin, Stephanie Fotsing, Austin Crinklaw, Gregory Seumois, Pejman Mohammadi, Mitchell Kronenberg, Bjoern Peters, Ferhat Ay, Pandurangan Vijayanand
Summary: This study utilized H3K27ac HiChIP analysis to identify promoter-interacting expression quantitative trait loci (pieQTLs) in five common immune cell types, showing the importance of these variants in gene regulation. Additionally, the study presents a method for functional eQTL discovery and provides insights into the relevance of noncoding variants for cell-specific gene regulation and disease association.
Article
Immunology
Anthony Kusnadi, Ciro Ramirez-Suastegui, Vicente Fajardo, Serena J. Chee, Benjamin J. Meckiff, Hayley Simon, Emanuela Pelosi, Gregory Seumois, Ferhat Ay, Pandurangan Vijayanand, Christian H. Ottensmeier
Summary: CD8(+) T cells in COVID-19 patients exhibit two distinct states – exhausted and non-exhausted, with non-exhausted cells in severe cases showing enhanced memory responses to SARS-CoV-2 infection.
SCIENCE IMMUNOLOGY
(2021)
Article
Developmental Biology
Ivelisse Cajigas, Abhijit Chakraborty, Madison Lynam, Kelsey R. Swyter, Monique Bastidas, Linden Collens, Hao Luo, Ferhat Ay, Jhumku D. Kohtz
Summary: The study reveals that Evf2 interacts with factors like Sox2 to regulate gene expression on chromosome 6 in mice. The interactions between Evf2 and Sox2 influence the activity of Dlx5/6UCE, ultimately affecting gene expression.
Article
Cell Biology
Yichen Wang, Lin Jia, Cong Wang, Zhonghua Du, Shilin Zhang, Lei Zhou, Xue Wen, Hui Li, Huiling Chen, Yuanyuan Nie, Dan Li, Shanshan Liu, Daniela Salgado Figueroa, Ferhat Ay, Wei Xu, Songling Zhang, Wei Li, Jiuwei Cui, Andrew R. Hoffman, Hui Guo, Ji-Fan Hu
Summary: Wang et al. identify Peln1 as a key chromatin long non-coding RNA that controls pluripotency exit and intrachromosomal looping in stem cells. Peln1 interacts with the Oct4 promoter, recruits DNMT3A, and alters the epigenotype to disrupt the intrachromosomal loop, leading to pluripotency exit. Peln1 also targets multiple pathway genes associated with stem cell self-renewal.
JOURNAL OF CELL BIOLOGY
(2022)
Article
Oncology
Zhixin Qiu, Linjie Zhao, Jia Z. Shen, Zhengyu Liang, Qiulian Wu, Kailin Yang, Lihua Min, Ryan C. Gimple, Qiyuan Yang, Shruti Bhargava, Chunyu Jin, Cheryl Kim, Denise Hinz, Deobrat Dixit, Jean A. Bernatchez, Briana C. Prager, Guoxin Zhang, Zhen Dong, Deguan Lv, Xujun Wang, Leo J. Y. Kim, Zhe Zhu, Katherine A. Jones, Ye Zheng, Xiuxing Wang, Jair L. Siqueira-Neto, Lukas Chavez, Xiang-Dong Fu, Charles Spruck, Jeremy N. Rich
Summary: This study identifies the YY1-CDK9 transcription elongation complex as a crucial factor in maintaining glioblastoma stemness and therapeutic resistance. Targeting this complex can activate interferon response, reduce regulatory T-cell infiltration, and enhance the efficacy of immune checkpoint therapy.
Article
Multidisciplinary Sciences
Simon Eschweiler, Ciro Ramirez-Suastegui, Yingcong Li, Emma King, Lindsey Chudley, Jaya Thomas, Oliver Wood, Adrian von Witzleben, Danielle Jeffrey, Katy McCann, Hayley Simon, Monalisa Mondal, Alice Wang, Martina Dicker, Elena Lopez-Guadamillas, Ting-Fang Chou, Nicola A. Dobbs, Louisa Essame, Gary Acton, Fiona Kelly, Gavin Halbert, Joseph J. Sacco, Andrew Graeme Schache, Richard Shaw, James Anthony McCaul, Claire Paterson, Joseph H. Davies, Peter A. Brennan, Rabindra P. Singh, Paul M. Loadman, William Wilson, Allan Hackshaw, Gregory Seumois, Klaus Okkenhaug, Gareth J. Thomas, Terry M. Jones, Ferhat Ay, Greg Friberg, Mitchell Kronenberg, Bart Vanhaesebroeck, Pandurangan Vijayanand, Christian H. Ottensmeier
Summary: This study assessed the effects of PI3K delta inhibitors in patients with head and neck cancer, finding that it reduced the number of regulatory T cells in tumors and enhanced the cytotoxic potential of tumor-infiltrating T cells. However, high doses of the inhibitors led to immune-related adverse events, indicating the need for alternative dosing regimens to limit toxicity.
Article
Immunology
Benjamin J. Schmiedel, Cristian Gonzalez-Colin, Vicente Fajardo, Job Rocha, Ariel Madrigal, Ciro Ramirez-Suastegui, Sourya Bhattacharyya, Hayley Simon, Jason A. Greenbaum, Bjoern Peters, Gregory Seumois, Ferhat Ay, Vivek Chandra, Pandurangan Vijayanand
Summary: This study reveals the specific effects of common genetic variants on gene expression in CD4(+)T cells, with these effects being most prominent in certain cell types. The study also identifies new gene associations for disease-risk variants and highlights the influence of biological sex on gene expression in CD4(+)T cell subsets.
SCIENCE IMMUNOLOGY
(2022)
Article
Allergy
Haruka Miki, William B. Kiosses, Mario C. Manresa, Rinkesh K. Gupta, Gurupreet S. Sethi, Rana Herro, Ricardo Da Silva Antunes, Paramita Dutta, Marina Miller, Kai Fung, Ashu Chawla, Katarzyna Dobaczewska, Ferhat Ay, David H. Broide, Alexei V. Tumanov, Michael Croft
Summary: This study found that signaling through lymphotoxin beta receptor and herpesvirus entry mediator from LIGHT directly controls the dysregulation of airway smooth muscle cells in asthma. By using animal models and in vitro experiments, it was discovered that these receptors play a crucial role in airway smooth muscle hyperresponsiveness and remodeling.
JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY
(2023)
Article
Multidisciplinary Sciences
Abhijit Chakraborty, Jeffrey G. Wang, Ferhat Ay
Summary: In this study, a method called dcHiC is introduced, which uses a multivariate distance measure to identify significant changes in compartmentalization among multiple contact maps. The effectiveness and sensitivity of dcHiC in detecting biologically relevant changes are demonstrated through evaluations on different datasets. dcHiC enables high-resolution compartment analysis and provides additional features such as browser visualization, differential interaction identification, and time-series clustering.
NATURE COMMUNICATIONS
(2022)
Article
Multidisciplinary Sciences
Konstantin Okonechnikov, Aylin Camgoez, Owen Chapman, Sameena Wani, Donglim Esther Park, Jens-Martin Huebner, Abhijit Chakraborty, Meghana Pagadala, Rosalind Bump, Sahaana Chandran, Katerina Kraft, Rocio Acuna-Hidalgo, Derek Reid, Kristin Sikkink, Monika Mauermann, Edwin F. Juarez, Anne Jenseit, James T. Robinson, Kristian W. Pajtler, Till Milde, Natalie Jaeger, Petra Fiesel, Ling Morgan, Sunita Sridhar, Nicole G. Coufal, Michael Levy, Denise Malicki, Charlotte Hobbs, Stephen Kingsmore, Shareef Nahas, Matija Snuderl, John Crawford, Robert J. Wechsler-Reya, Tom Belle Davidson, Jennifer Cotter, George Michaiel, Gudrun Fleischhack, Stefan Mundlos, Anthony Schmitt, Hannah Carter, Kulandaimanuvel Antony Michealraj, Sachin A. Kumar, Michael D. Taylor, Jeremy Rich, Frank Buchholz, Jill P. Mesirov, Stefan M. Pfister, Ferhat Ay, Jesse R. Dixon, Marcel Kool, Lukas Chavez
Summary: This study investigates the chromosomal conformations and regulatory mechanisms associated with aberrant gene expression in ependymoma tumors. The researchers identified new topologically associating domains, group-specific chromatin loops, and the replacement of CTCF insulators by DNA hyper-methylation. Inhibition experiments confirmed that genes implicated by these 3D genome conformations are essential for the survival of patient-derived ependymoma models.
NATURE COMMUNICATIONS
(2023)
Article
Multidisciplinary Sciences
Meghana Pagadala, Timothy J. Sears, Victoria H. Wu, Eva Perez-Guijarro, Hyo Kim, Andrea Castro, James V. Talwar, Cristian Gonzalez-Colin, Steven Cao, Benjamin J. Schmiedel, Shervin Goudarzi, Divya Kirani, Jessica Au, Tongwu Zhang, Teresa Landi, Rany M. Salem, Gerald P. Morris, Olivier Harismendy, Sandip Pravin Patel, Ludmil B. Alexandrov, Jill P. Mesirov, Maurizio Zanetti, Chi-Ping Day, Chun Chieh Fan, Wesley K. Thompson, Glenn Merlino, J. Silvio Gutkind, Pandurangan Vijayanand, Hannah Carter
Summary: Understanding how host genetics affects the tumor immune microenvironment (TIME) is essential for personalized cancer screening and treatment strategies. A study analyzed the eQTLs affecting TIME and found that they are enriched in areas of active transcription and associated with gene expression in specific immune cell subsets. Polygenic score models built with TIME eQTLs can stratify cancer risk, survival, and immune checkpoint blockade (ICB) response. Inhibiting the CTSS gene, which is implicated by the polygenic models, slows tumor growth and extends survival, suggesting the potential of integrating genetic factors and TIME characteristics for immunotherapy targets.
NATURE COMMUNICATIONS
(2023)
Article
Immunology
Shilpi Chandra, Gabriel Ascui, Thomas Riffelmacher, Ashu Chawla, Ciro Ramirez-Suastegui, Viankail C. Castelan, Gregory Seumois, Hayley Simon, Mallory P. Murray, Goo-Young Seo, Ashmitaa L. R. Premlal, Benjamin Schmiedel, Greet Verstichel, Yingcong Li, Chia-Hao Lin, Jason Greenbaum, John Lamberti, Raghav Murthy, John Nigro, Hilde Cheroutre, Christian H. Ottensmeier, Stephen M. Hedrick, Li-Fan Lu, Pandurangan Vijayanand, Mitchell Kronenberg
Summary: This study characterized the different populations of MAIT cells in mice and humans using single-cell RNA sequencing and other analyses. The study found that MAIT cells in different organs and tissues exhibit different transcriptomes and metabolic states. The study also identified environmental influences on MAIT cell subsets and function.
SCIENCE IMMUNOLOGY
(2023)
Meeting Abstract
Immunology
Rinkesh Kumar Gupta, Donald Gracias, Daniela Salgado Figueroa, Haruka Miki, Jacqueline Miller, Kai Fung, Ferhat Ay, Linda C. Burkly, Michael Croft
JOURNAL OF IMMUNOLOGY
(2022)
