Article
Cell Biology
Shah Md Toufiqur Rahman, Mohammad Aqdas, Erik W. Martin, Francesco Tomassoni Ardori, Preeyaporn Songkiatisak, Kyu-Seon Oh, Stefan Uderhardt, Sangwon Yun, Quia C. Claybourne, Ross A. McDevitt, Valentina Greco, Ronald N. Germain, Lino Tessarollo, Myong-Hee Sung
Summary: This study introduces reporter mice with fluorescently labeled RelA and c-Rel proteins for real-time imaging of NF-KB signaling. The results show that quantitative features of signaling reflect different activating ligands, cell types, and age-related changes. Unexpectedly, the RelA:c-Rel heterodimer is depleted in the nuclei of stimulated cells.
Article
Biochemistry & Molecular Biology
Jan P. Dumanski, Jonatan Halvardson, Hanna Davies, Edyta Rychlicka-Buniowska, Jonas Mattisson, Behrooz Torabi Moghadam, Noemi Nagy, Kazimierz Weglarczyk, Karolina Bukowska-Strakova, Marcus Danielsson, Pawel Olszewski, Arkadiusz Piotrowski, Erin Oerton, Aleksandra Ambicka, Marcin Przewoznik, Lukasz Belch, Tomasz Grodzicki, Piotr L. Chlosta, Stefan Imreh, Vilmantas Giedraitis, Lena Kilander, Jessica Nordlund, Adam Ameur, Ulf Gyllensten, Asa Johansson, Alicja Jozkowicz, Maciej Siedlar, Alicja Klich-Raczka, Janusz Jaszczynski, Stefan Enroth, Jaroslaw Baran, Martin Ingelsson, John R. B. Perry, Janusz Rys, Lars A. Forsberg
Summary: Epidemiological investigations have shown that mosaic loss of chromosome Y (LOY) in leukocytes is associated with increased mortality and morbidity in men. Studies on sorted and single cells revealed significant variations in the presence of LOY across cell types and individuals, suggesting potential pleiotropic effects on gene expression and immune function.
CELLULAR AND MOLECULAR LIFE SCIENCES
(2021)
Review
Medicine, General & Internal
Iosif Papafragkos, Efrosyni Markaki, Christina Kalpadakis, Panayotis Verginis
Summary: Myeloid-derived suppressor cells (MDSCs) are potent regulators of the immune system, playing a role in cancer but their specific contribution to lymphomas remains unclear. This review focuses on MDSCs in lymphomas, discussing literature and lessons learned from animal models, and highlights future research directions and challenges in understanding the immune system complexities in malignancies.
JOURNAL OF CLINICAL MEDICINE
(2021)
Review
Biochemistry & Molecular Biology
Ching-Chuan Hsieh, Cheng-Chih Chang, Yung-Chien Hsu, Chun-Liang Lin
Summary: In the development of diabetic kidney disease, the dysregulation of glomerular cell types is crucial, and MDSCs exhibit anti-inflammatory activities that help improve renal fibrosis in diabetic mice.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Immunology
Min-Jung Park, Jin-Ah Baek, Jeong Won Choi, Se Gwang Jang, Da-Som Kim, Sung-Hwan Park, Mi-La Cho, Seung-Ki Kwok
Summary: This study found that mRNA levels of immunosuppressive molecules were significantly decreased in MDSCs from lupus patients and mice, while PD-L1 expressing MDSCs from control mice more potently expanded regulatory T cells and regulatory B cells. Therapy with PD-L1 expressing MDSCs reduced autoantibody levels, improved renal pathology in two animal models of lupus, and suppressed pathogenic immune cells. These results suggest that PD-L1 expressing MDSCs could be a promising therapeutic strategy for systemic autoimmune diseases.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Biochemistry & Molecular Biology
F. Barrachina, K. Ottino, L. J. Tu, R. J. Soberman, D. Brown, S. Breton, M. A. Battistone
Summary: Mononuclear phagocytes (MPs) are important for maintaining immunological balance in the urogenital tract. The CX3CR1 receptor plays a crucial role in antigen sampling and processing in the murine epididymis. This study shows that CX3CR1 deficiency impairs the immune response during epididymitis, highlighting the role of MPs in maintaining epididymal homeostasis and revealing potential diagnostic and therapeutic approaches for male infertility and epididymitis.
CELLULAR AND MOLECULAR LIFE SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Anthony DiNatale, Ramanpreet Kaur, Chen Qian, Jieyi Zhang, Michael Marchioli, Darin Ipe, Maria Castelli, Chris M. McNair, Gaurav Kumar, Olimpia Meucci, Alessandro Fatatis
Summary: Metastasis-initiating cells (MICs) with stem cell-like features, high expression of CX3CR1, OCT4a, and NANOG, are associated with metastasis, chemotherapy resistance, and patient mortality. These cells can continuously emerge from non-stem cancer cells, and CX3CR1 expression confers resistance to docetaxel. CX3CR1 is identified as a novel marker of stem-like tumor cells and may serve as a potential therapeutic target for preventing or containing metastasis initiation.
Article
Immunology
Timea Sereny-Litvai, Anna Bajnok, Viktoria Temesfoi, Jasper Norenberg, Greta Pham-Dobor, Ambrus Kaposi, Akos Varnagy, Kalman Kovacs, Sandor Pentek, Tamas Koszegi, Emese Mezosi, Timea Berki
Summary: Research shows that B cell subsets of ATA+, infertile, euthyroid patients have higher Ca2+ flux response to BCR stimulation, potentially reflecting altered immune function; After levothyroxine treatment, patients exhibit decreased prevalence of CD25(+) B cells and lower basal Ca2+ level.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Immunology
Robert W. Maul, Michelle D. Catalina, Varsha Kumar, Prathyusha Bachali, Amrie C. Grammer, Shu Wang, William Yang, Sarfaraz Hasni, Rachel Ettinger, Peter E. Lipsky, Patricia J. Gearhart
Summary: A distinct population of B cells marked by elevated CD11c expression was identified in patients with systemic lupus erythematosus (SLE), exhibiting unique characteristics in gene expression and IgH repertoire composition. These CD11c(hi) B cells showed similarities with some germinal center transcripts but distinct from conventional B cell subsets, suggesting a potential role in autoimmune responses. The findings suggest a potential link between defects in negative selection in germinal centers and the development of autoimmune diseases.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Oncology
Yu Chen, Yanquan Xu, Huakan Zhao, Yu Zhou, Jiangang Zhang, Juan Lei, Lei Wu, Mingyue Zhou, Jingchun Wang, Shuai Yang, Xiao Zhang, Guifang Yan, Yongsheng Li
Summary: Cancer immunotherapy targeting myeloid-derived suppressor cells (MDSCs) is a promising anti-cancer strategy. This study explored the regulatory mechanisms of cholesterol metabolic reprogramming in MDSCs and found that cholesterol deficiency increased the immunosuppressive activity of MDSCs. Mechanistically, cholesterol elimination induced nuclear accumulation of LXR beta and enhanced the binding of LXR beta-RXR alpha on Arg1 promoter. Furthermore, itraconazole improved MDSC immunosuppressive activity and promoted tumor growth by inhibiting the RIPK3-AKT-mTORC1 pathway and impeding cholesterol synthesis.
Article
Surgery
Qiang Fu, Kang Mi Lee, Guoli Huai, Kevin Deng, Divyansh Agarwal, Charles G. Rickert, Noel Feeney, Rudy Matheson, Hongji Yang, Christian LeGuern, Shaoping Deng, James F. Markmann
Summary: Regulatory B cells (Bregs) have been found to have potential as anti-rejection therapy in organ transplantation, particularly Bregs-TLR cells stimulated by TLR ligands that can prevent allograft rejection. These Bregs-TLR cells can suppress B cell proliferation, leading to a decline in antibody responses to antigenically disparate skin grafts. Additionally, the specificity of Breg BCR plays a crucial role in regulation.
AMERICAN JOURNAL OF TRANSPLANTATION
(2021)
Article
Immunology
Kevin Bassler, Wataru Fujii, Theodore S. Kapellos, Erika Dudkin, Nico Reusch, Ari Horne, Benedikt Reiz, Malte D. Luecken, Collins Osei-Sarpong, Stefanie Warnat-Herresthal, Lorenzo Bonaguro, Jonas Schulte-Schrepping, Allon Wagner, Patrick Guenther, Carmen Pizarro, Tina Schreiber, Rainer Knoll, Lisa Holsten, Charlotte Kroeger, Elena De Domenico, Matthias Becker, Kristian Haendler, Christian T. Wohnhaas, Florian Baumgartner, Meike Koehler, Heidi Theis, Michael Kraut, Marc H. Wadsworth, Travis K. Hughes, Humberto J. Ferreira, Emily Hinkley, Ines H. Kaltheuner, Matthias Geyer, Christoph Thiele, Alex K. Shalek, Andreas Feisst, Daniel Thomas, Henning Dickten, Marc Beyer, Patrick Baum, Nir Yosef, Anna C. Aschenbrenner, Thomas Ulas, Jan Hasenauer, Fabian J. Theis, Dirk Skowasch, Joachim L. Schultze
Summary: Despite the high prevalence of COPD, the cellular and molecular mechanisms of the disease remain poorly understood. This study investigates the changes in cellular and molecular compositions in the alveolar space and peripheral blood of COPD patients compared to controls. The findings suggest that myeloid cells, including invading monocytes and proliferating macrophages, are increased in COPD. Computational modeling predicts TGF-beta 1 as a major regulator of transcriptional changes in alveolar macrophages of COPD patients. Functionally, macrophages in COPD exhibit impaired immune activation.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Anatomy & Morphology
Haozhong Huang, Peile Ren, Yiwei Zhao, Huimin Weng, Chunsen Jia, Fengxu Yu, Yongmei Nie
Summary: Low shear stress (LSS) can induce the development of atherosclerosis, but the molecular mechanisms of LSS-induced inflammation are still unclear. This study comprehensively identified the molecular circuitry involved in LSS-induced inflammation in human umbilical vein endothelial cells (HUVECs) through protein profiling and cell function experiments. The results showed that LSS increased the expression of CX3CR1, nucleusP65, ICAM-1, VCAM-1, and IL-6, while decreasing the expression of cytosolic P65 and I kappa B in HUVECs. CX3CR1 sh-RNA and NF-kappa B inhibitors could abrogate the effect of LSS-induced inflammation. Monocyte adhesion assay and scratch test revealed that LSS promotes monocyte adhesion and cell migration, which can be reversed by CX3CR1 sh-RNA and NF-kappa B inhibitors. This study suggests that the signaling pathways activated by LSS in endothelial cells may serve as therapeutic targets for atherosclerosis.
Article
Medicine, Research & Experimental
Aaron L. Sarver, Chencheng Xie, Megan J. Riddle, Colleen L. Forster, Xiaohong Wang, Huarui Lu, Wyatt Wagner, Jakub Tolar, Timothy C. Hallstrom
Summary: This study identified a unique immune gene expression signature in early-onset retinoblastoma, leading to an increase in immune cell infiltration and a decrease in tumor cell proliferation. The immune signature was also observed in aggressive tumors in mice and humans, correlating with lower proliferative capacity.
LABORATORY INVESTIGATION
(2021)
Article
Immunology
Anthonie Johan Zwijnenburg, Jyoti Pokharel, Renata Varnait, Wenning Zheng, Elena Hoffer, Iman Shryki, Natalia Ramirez Comet, Marcus Ehrstrom, Sara Gredmark-Russ, Liv Eidsmo, Carmen Gerlach
Summary: This study aims to identify surface markers that reflect the gradient nature of CD8+ T cell differentiation and to delineate functionally comparable states in mice and humans. The researchers found that graded expression of CX3CR1 is correlated with CD8+ T cell differentiation gradient, and it accurately captures the high-dimensional T cell differentiation continuum. Additionally, CX3CR1 expression can delineate states with comparable properties in virus-specific CD8+ T cells in both species.
