Article
Biology
Julie Y. Zhou, Carlos A. Alvarez, Brian A. Cobb
Summary: Cells integrate concurrent signaling initiated by different cytokines to produce specific responses, and the combinatorial effects of different cytokines can lead to distinct biological outcomes, understanding this signaling pathway is crucial for addressing diseases.
Article
Multidisciplinary Sciences
Huishan Tao, Yun Pan, Shuai Chu, Lei Li, Jinhai Xie, Peng Wang, Shimeng Zhang, Srija Reddy, John W. Sleasman, Xiao-Ping Zhong
Summary: MAIT cells are important in immunity and diseases. An IL-1 beta/IL-23/mTORC2 axis is crucial for inducing IL-17-producing MAIT17, while an IL-2/IL-15/mTORC1 axis is important for the homeostasis of IFN-gamma-producing MAIT1.
NATURE COMMUNICATIONS
(2021)
Article
Cell Biology
Ryma Toumi, Yevgeniy Yuzefpolskiy, Adithya Vegaraju, Hanxi Xiao, Kendall A. Smith, Surojit Sarkar, Vandana Kalia
Summary: This study demonstrates that paracrine IL-2 is crucial for optimal primary expansion, effector and memory differentiation, and metabolic function in CD8 T cells, while autocrine IL-2 is uniquely required during primary expansion to program robust secondary expansion potential in memory-fated cells. Additionally, IL-2 production by antigen-specific CD8 T cells is largely independent of CD4 licensing of dendritic cells in inflammatory infections with robust DC activation.
Review
Immunology
Juliane Lokau, Lynn M. Petasch, Christoph Garbers
Summary: Interleukin-2 (IL-2) is an important regulator of immune response, and its signaling involves three receptors (IL-2Rα, IL-2Rβ, and IL-2Rγ). Soluble form of IL-2Rα (sIL-2Rα) is present in the blood and increased under pathological conditions. The effects of sIL-2Rα on IL-2 function and immune responses are not fully understood.
Article
Gastroenterology & Hepatology
Jazib Uddin, Sunil Tomar, Ankit Sharma, Lisa Waggoner, Varsha Ganesan, Sahiti Marella, Yanfen Yang, Taeko Noah, Simone Vanoni, Andrew Patterson, Chang Zeng, Paul S. Foster, Rodney Newberry, Shrinivas Bishu, John Y. Kao, Michael J. Rosen, Lee Denson, Philip D. King, Kasper Hoebe, Senad Divanovic, Ariel Munitz, Simon P. Hogan
Summary: The inhibitory receptor PIR-B plays a role in regulating CD4(+) IL17a(+) T-cell pathogenic memory responses, modulating chronic intestinal inflammatory responses and the development of colitis. The downstream axis involving PIR-B, Src-homology region 2 domain-containing phosphatase-1/2, and mammalian target of rapamycin complex 1 signaling is important for CD4(+) IL17a(+) cell survival. Furthermore, transcriptional signatures associated with Th17 cells and tissue resident memory networks were enriched in PIR-B+ murine CD4(+) T cells and human CD4(+) T cells expressing LILRB3, demonstrating the potential significance of PIR-B and its human homologue in inflammatory diseases.
CELLULAR AND MOLECULAR GASTROENTEROLOGY AND HEPATOLOGY
(2021)
Article
Immunology
Shining Ma, Michelle So, Aazam Ghelani, Rohith Srivas, Anupama Sahoo, Robyn Hall, Wenjun Liu, Hao Wu, Sherman Yu, Shiping Lu, Elly Song, Taryn Cariaga, Marcus Soto, Hong Zhou, Chi-Ming Li, Ashutosh Chaudhry, Xin Luo, Sue J. Sohn
Summary: This study demonstrates that attenuated IL-2 muteins have a stronger effect on Treg activation and conversion, and can reduce the dependence on TCR signal. These findings suggest the potential therapeutic use of attenuated IL-2 muteins for inflammatory diseases.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Multidisciplinary Sciences
Narges Aghaallaei, Advaita M. Dick, Erika Tsingos, Daigo Inoue, Eva Hasel, Thomas Thumberger, Atsushi Toyoda, Maria Leptin, Joachim Wittbrodt, Baubak Bajoghli
Summary: The study in medaka fish reveals that progenitors first enter a thymic niche favoring the development of gamma delta T cells, and the gradients of interleukin-7 and Ccl25a in the niche influence the lineage outcome. This previously unknown mechanism determines the proportion of alpha beta/gamma delta lineages within species.
Article
Medicine, Research & Experimental
Praveen Prakhar, Jaylene Alvarez-DelValle, Hilary Keller, Assiatu Crossman, Xuguang Tai, Yoo Kyoung Park, Jung-Hyun Park
Summary: Foxp3(+) Tregs in the small intestine epithelium do not require IL-2 for survival and effector functions, exhibiting an independent mechanism and potent suppressor function.
Article
Immunology
David L. Owen, Rebecca S. La Rue, Sarah A. Munro, Michael A. Farrar
Summary: Recent studies have revealed multiple stages of regulatory T cell development in the thymus, with both CD25+ T cell progenitors and FOXP3lo T cell progenitors undergoing agonist-activated states and transitional stages before differentiating into mature T cells. CD25+ T cell progenitors were found to be the major source of IL-2 required for the conversion of progenitors into mature T cells. Additionally, thymic resident regulatory T cells were found to be heterogeneous and exhibit the most diverse T cell receptor repertoire among CD4 single-positive thymocytes.
JOURNAL OF IMMUNOLOGY
(2022)
Review
Immunology
Harikesh S. Wong, Ronald N. Germain
Summary: Mature T cells must distinguish between foreign and self-antigens to promote host defense while limiting autoimmunity. The discrimination occurs reproducibly at a higher-level boundary post-activation, which is governed by coordinated communication among at least three cell types and includes negative feedback from regulatory T cells (Tregs). The nonlinearities within this system can amplify subtle imbalances in a single cell type's functional state, altering the threshold for productive T cell responses and autoimmune disease risk.
TRENDS IN IMMUNOLOGY
(2021)
Review
Cardiac & Cardiovascular Systems
Akinori Higaki, Ahmad U. M. Mahmoud, Pierre Paradis, Ernesto L. Schiffrin
Summary: Hypertension is partially mediated by immune mechanisms, with IL-23 and IL-17 playing important roles. The IL-23/IL-17 axis has not been a major therapeutic target for hypertension treatment, but shows potential for targeting therapy.
CARDIOVASCULAR RESEARCH
(2021)
Article
Immunology
Coco Chu, Christopher N. Parkhurst, Wen Zhang, Lei Zhou, Hiroshi Yano, Mohammad Arifuzzaman, David Artis
Summary: ILC2s up-regulate ChAT and express AChRs after infection or treatment, with ACh administration promoting cytokine production and helminth expulsion. Deficiency of ChAT in ILC2s leads to impaired immunity.
SCIENCE IMMUNOLOGY
(2021)
Article
Fisheries
Mengmeng Zhao, Jing Xing, Xiaoqian Tang, Xiuzhen Sheng, Heng Chi, Wenbin Zhan
Summary: By cloning interleukin-2 receptor subunit gamma (IL-2R gamma) in flounder and producing specific antibodies, this study characterized the expression of flounder IL-2R gamma (fIL-2R gamma) at transcriptional and cellular levels and investigated its interaction with flounder IL-2 (fIL-2). The results demonstrated that fIL-2R gamma was expressed on both T and B lymphocytes and the binding of fIL-2R gamma and fIL-2 activated CD4 T lymphocytes.
FISH & SHELLFISH IMMUNOLOGY
(2022)
Article
Cell Biology
Ali M. Farhat, Adam C. Weiner, Cori Posner, Zoe S. Kim, Brian Orcutt-Jahns, Scott M. Carlson, Aaron S. Meyer
Summary: The study introduces a binding reaction model for common gamma-chain cytokines, enabling quantitative predictions of cell type-specific responses to natural and engineered cytokines. Tensor factorization is shown to be a powerful tool in visualizing changes in the input-output behavior of the cytokine family across various parameters like time, cell types, ligands, and concentrations. This results in a more accurate ligand response model validated across immune cell types, as well as a general approach for generating interpretable guidelines for manipulating cell type-specific targeting of engineered ligands.
Review
Cell Biology
Anselm Mak
Summary: The complexities of T cells in SLE and the potential role of IL-2 in the pathophysiological process of SLE are discussed in this article. Low-dose IL-2 administration shows promise as a therapeutic approach for SLE.
Article
Allergy
Md Ashik Ullah, Cristina T. Vicente, Natasha Collinson, Bodie Curren, Md Al Amin Sikder, Ismail Sebina, Jennifer Simpson, Antiopi Varelias, Jonathan A. Lindquist, Manuel A. R. Ferreira, Simon Phipps
Article
Multidisciplinary Sciences
Veronika Kozlova, Aneta Ledererova, Adriana Ladungova, Helena Peschelova, Pavlina Janovska, Aleksander Slusarczyk, Joanna Domagala, Pavel Kopcil, Viera Vakulova, Jan Oppelt, Vitezslav Bryja, Michael Doubek, Jiri Mayer, Sarka Pospisilova, Michal Smida
Article
Rheumatology
Stefan Meltendorf, Hang Fu, Mandy Pierau, Jonathan A. Lindquist, Stephanie Finzel, Peter R. Mertens, Steffi Gieseler-Halbach, Andreas Ambach, Ulrich Thomas, Holger Lingel, Reinhard E. Voll, Monika C. Brunner-Weinzierl
ARTHRITIS & RHEUMATOLOGY
(2020)
Article
Oncology
Veronika Mancikova, Helena Peschelova, Veronika Kozlova, Aneta Ledererova, Adriana Ladungova, Jan Verner, Tomas Loja, Frantisek Folber, Jiri Mayer, Sarka Pospisilova, Michal Smida
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2020)
Article
Oncology
Aneri Shah, Carlos Plaza-Sirvent, Soenke Weinert, Joern H. Buchbinder, Inna N. Lavrik, Peter R. Mertens, Ingo Schmitz, Jonathan A. Lindquist
Article
Biochemistry & Molecular Biology
Christopher L. Hessman, Josephine Hildebrandt, Aneri Shah, Sabine Brandt, Antonia Bock, Bjoern C. Frye, Ute Raffetseder, Robert Geffers, Monika C. Brunner-Weinzierl, Berend Isermann, Peter R. Mertens, Jonathan A. Lindquist
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2020)
Article
Cell Biology
Katerina Stano Kozubik, Lenka Radova, Kamila Reblova, Michal Smida, Marketa Zaliova Kubricanova, Jiri Baloun, Michaela Pesova, Zuzana Vrzalova, Frantisek Folber, Sona Mejstrikova, Sarka Pospisilova, Michael Doubek
Summary: Germline mutations in the ETV6 gene cause inherited thrombocytopenia and predispose to leukemia. Functional analysis of the ETV6W380R mutation revealed impaired DNA binding, affecting the nuclear localization and transcriptional repression activity of the ETV6 protein. The ALL in this family may have been caused by diverse mechanisms, including high-hyperdiploidy, somatic deletion of the IKZF1 gene, or somatic mutations of other genes found by exome sequencing.
Article
Biochemistry & Molecular Biology
Anja Bernhardt, Saskia Haeberer, JingJing Xu, Hannah Damerau, Johannes Steffen, Charlotte Reichardt, Katharina Wolters, Hannes Steffen, Berend Isermann, Katrin Borucki, Nadine Artelt, Nicole Endlich, Renata Kozyraki, Sabine Brandt, Jonathan A. Lindquist, Peter R. Mertens
Summary: High salt diet can lead to blood pressure elevations, weight gain, and onset of diabetes, with compensatory mechanisms in the kidney maintaining balance. The study highlights the protective role of YB-1 in tubular cells under HSD conditions, regulating reabsorption thresholds for amino acids, proteins, and glucose.
Review
Biochemistry & Molecular Biology
Veronika Mancikova, Michal Smida
Summary: CAR T-cell therapy has shown remarkable remissions in difficult-to-treat patients with B-cell malignancies, but the efficacy in chronic lymphocytic leukemia patients is the lowest among B-cell tumors, requiring further investigation into treatment mechanisms and failure reasons.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Biochemistry & Molecular Biology
Violeta Stojanovska, Aneri Shah, Katja Woidacki, Florence Fischer, Mario Bauer, Jonathan A. Lindquist, Peter R. Mertens, Ana C. Zenclussen
Summary: YB-1 plays a crucial role in trophoblast cell functioning, with over-expression or exposure leading to enhanced proliferation, while its knockdown leads to proliferative disadvantage.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Review
Oncology
Aneri Shah, Jonathan A. Lindquist, Lars Rosendahl, Ingo Schmitz, Peter R. Mertens
Summary: YB-1 is a RNA binding protein involved in various cellular processes, its activation is associated with NF-kappa B and can affect the inflammatory response and cell survival mechanisms.
Article
Urology & Nephrology
Sabine Brandt, Anja Fischer, Carla Kreutze, Dorothea Hempel, Xenia Gorny, Florian G. Scurt, Delia L. Balaru, Peter Bartsch, Anja Bernhardt, Stefanie M. Bode-Boeger, Matthias Girndt, Roman Fiedler, Berend Isermann, Jonathan A. Lindquist, Peter R. Mertens
Summary: In end-stage renal disease, elevated levels of midkine are associated with high cardiovascular risk and endothelial damage. Increased midkine levels are correlated with hypervolemia and are associated with cardiovascular events and mortality rates.
INTERNATIONAL UROLOGY AND NEPHROLOGY
(2022)
Article
Cell Biology
Jonathan A. Lindquist, Anja Bernhardt, Charlotte Reichardt, Eva Sauter, Sabine Brandt, Rajiv Rana, Maja T. Lindenmeyer, Lars Philipsen, Berend Isermann, Cheng Zhu, Peter R. Mertens
Summary: DNA-binding protein A (DbpA), a member of the Y-box family, plays a role in transcription and translation by binding and regulating mRNA. In a mouse model of kidney disease, DbpA expression was induced in the renal interstitium. Deficiency of the Ybx3 gene resulted in protection against tissue injury and reduced immune cell infiltration and extracellular matrix deposition. Our RNAseq data showed that Ybx3 is expressed by activated fibroblasts in the renal interstitium. These findings suggest that targeting DbpA may be a potential therapeutic option for slowing down kidney disease progression.
Meeting Abstract
Gastroenterology & Hepatology
Tao Lin, Jonathan A. Lindquist, Peter Rene Mertens, Matthias Ebert, Steven Dooley, Jun Li, Stefan Munker, Honglei Weng
JOURNAL OF HEPATOLOGY
(2022)
Meeting Abstract
Immunology
Stefan Meltendorf, Hang Fu, Mandy Pierau, Jonathan A. Lindquist, Stephanie Fienzel, Peter R. Mertens, Steffi Gieseler Halbach, Andreas Ambach, Ulrich Thomas, Holger Lingel, Reinhard E. Voll, Monika C. Brunner Weinzierl
EUROPEAN JOURNAL OF IMMUNOLOGY
(2021)