Article
Multidisciplinary Sciences
Pernille Kristine Fisker Christensen, Axel Kornerup Hansen, Sren Skov, Britta Cathrina Martel, Jesper Larsen, Maria Helena Hoyer-Hansen, Janne Koch
Summary: In this study, the researchers investigated whether human immune cells played a role in the induction of psoriasis-like skin inflammation in hFlt3L-boosted BRGSF-HIS mice treated with IMQ. The results showed that although the mice exhibited clinical skin inflammation, increased epidermal thickness, and influx of human immune cells, the human immune response was not significant. Instead, the main driving cellular mechanisms were of murine origin, as indicated by the increased number of murine neutrophils and cytokines and chemokines in the skin and systemically after IMQ application.
Article
Immunology
Seul Hye Ryu, Hyun Soo Shin, Hye Hyeon Eum, Ji Soo Park, Wanho Choi, Hye Young Na, Hyunju In, Tae-Gyun Kim, Sejung Park, Soomin Hwang, Moah Sohn, Eun-Do Kim, Kyoung Yul Seo, Hae-Ock Lee, Min-Geol Lee, Min Kyung Chu, Chae Gyu Park
Summary: Dendritic cells (DCs) play a crucial role in initiating adaptive immunity. Injecting granulocyte macrophage-colony stimulating factor (GM-CSF) can generate a distinct subset of DCs called GMiDCs in the spleen, which have superior antigen-presenting ability and can activate CD4(+) T cells and polarize Th2 cells. The generation of GMiDCs depends on the expression of GM-CSF receptor, and they can also be found in other tissues and during chronic allergic inflammation. This study provides important insights into the development and immune regulation of DCs.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Multidisciplinary Sciences
Chiara Bernardi, Gaetan Maurer, Tao Ye, Patricia Marchal, Bernard Jost, Manuela Wissler, Ulrich Maurer, Philippe Kastner, Susan Chan, Celine Charvet
Summary: The transcription factor Ikaros regulates gene expression and chromatin accessibility in T cells to suppress the expression of pathogenic genes, particularly GM-CSF. This mechanism plays a critical role in preventing excessive GM-CSF expression in T cells.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Immunology
Javad Rasouli, Giacomo Casella, Weifeng Zhang, Dan Xiao, Gaurav Kumar, Paolo Fortina, Guang-Xian Zhang, Bogoljub Ciric, Abdolmohamad Rostami
Summary: GM-CSF-producing T helper cells, known as ThGM cells, have been found to play a crucial role in autoimmune diseases. ThGM cells express TNF, IL-2, and IL-3 cytokines, but lack the master transcription factors and signature cytokines of commonly recognized Th cell lineages. ThGM cells are highly encephalitogenic in a mouse model of multiple sclerosis, and they can switch their phenotype to Th1 in response to IL-12. This study shows that RUNX3 transcription factor, in addition to T-bet, contributes to the Th1 switch of ThGM cells. ThGM cells are a non-polarized subset of Th cells with lineage characteristics and express transcription factors that inhibit the development of other Th lineages.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Allergy
Samuel Philip Nobs, Lea Pohlmeier, Fengqi Li, Merve Kayhan, Burkhard Becher, Manfred Kopf
Summary: Through experimental animal models, it was found that the GM-CSF signaling pathway plays a key role in regulating the accumulation of neutrophils in the lungs in chronic asthma, thereby promoting the development of airway hyperresponsiveness in chronic diseases.
JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY
(2021)
Article
Medicine, Research & Experimental
Adam L. Burrack, Zoe C. Schmiechen, Michael T. Patterson, Ebony A. Miller, Ellen J. Spartz, Meagan R. Rollins, Jackson F. Raynor, Jason S. Mitchell, Tsuneyasu Kaisho, Brian T. Fife, Ingunn M. Stromnes
Summary: We investigated the differential impact of myeloid subsets on immunity to pancreatic ductal adenocarcinoma (PDA). Our study demonstrates that tumor antigenicity shapes the composition and functionality of myeloid cells. The therapeutic effectiveness of adoptive T cell therapy or programmed cell death ligand 1 blockade relies on the presence of type 1 dendritic cells (cDC1), which support the survival and function of antitumor T cells. Our research highlights the essential role of cDC1s in sustaining effective antitumor T cells and reveals differential roles for cDC1s and monocytes/macrophages in guiding T cell fate and immunotherapy response.
Article
Medicine, General & Internal
Annette D. D. Wagner, Ulrike Wittkop, Jessica Thalmann, Tina Willmen, Vega Goedecke, Justyna Hodam, Simon Ronicke, Martin Zenke
Summary: In patients with GCA, glucocorticoid therapy leads to a rapid reduction in the number of DCs, an increase in apoptotic cells, and a decrease in the expression of mediators for cell migration. These findings suggest GM-CSF as a potential therapeutic target for GCA.
FRONTIERS IN MEDICINE
(2021)
Article
Rheumatology
Meilang Xue, Haiyan Lin, Hai Po Helena Liang, Lara Bereza-Malcolm, Tom Lynch, Premarani Sinnathurai, Hartmut Weiler, Christopher Jackson, Lyn March
Summary: This study found that the deficiency of EPCR can ameliorate the onset and development of CIA by inhibiting the activation and migration of pathogenic Th cells and DCs. Therefore, targeting EPCR may constitute a novel strategy for future RA treatment.
Article
Oncology
Tatiana Smirnova, Caroline Spertini, Olivier Spertini
Summary: The interaction between macrophages and leukemia cells plays a crucial role in promoting leukemia cell survival and resistance to therapy. Inhibiting the CSF1 receptor can reprogram macrophage polarization, increase leukemia cell apoptosis, and improve sensitivity to treatment. Targeting the microenvironment, specifically macrophages and the CSF1 receptor, may be a novel approach for acute myeloid leukemia therapy to address issues of relapse.
Article
Biotechnology & Applied Microbiology
Rui Chen, Yujie Li, Yangyang Zhuang, Yiming Zhang, Hailong Wu, Tao Lin, Shixuan Chen
Summary: This study combines GM-CSF and 3D nanofiber scaffolds to promote tissue regeneration. Through subcutaneous implantation in humanized mice, it was found that GM-CSF could accelerate cell migration and cytokine release, and ultimately enhance tissue regeneration. Therefore, GM-CSF loaded 3D nanofiber scaffolds have potential applications in tissue regeneration.
FRONTIERS IN BIOENGINEERING AND BIOTECHNOLOGY
(2023)
Article
Oncology
Veronica L. Nagle, Charli Ann J. Hertz, Kelly E. Henry, Maya S. Graham, Carl Campos, Nagavarakishore Pillarsetty, Andrea Schietinger, Ingo K. Mellinghoff, Jason S. Lewis
Summary: This study explores the use of anti-human-CD4 minibody for antibody-based PET to visualize human CD4(+) T cells. Through in vitro and in vivo experiments, it is found that this method can accurately detect CD4(+) T cells without impacting their abundance, proliferation, and activation state. In humanized mice, this method can also visualize the distribution of CD4(+) T cells in peripheral tissues and brain tumors.
MOLECULAR CANCER THERAPEUTICS
(2022)
Article
Biotechnology & Applied Microbiology
Torki Alothaimeen, Evan Trus, Sameh Basta, Katrina Gee
Summary: The study reveals differences in macrophage development and cytokine expression between M-CSF and GM-CSF cells after virus infection. While R848-induced cytokine expression is enhanced, signaling molecule activation is decreased in LCMV-infected macrophages. Interestingly, TLR7 expression is maintained at higher levels in M-CSF cells compared to GM-CSF.
JOURNAL OF GENERAL VIROLOGY
(2021)
Article
Multidisciplinary Sciences
Xiu Teng, Li-Ping Li, Meng Tang, Hui-Fang Li, Xiang-Yi Ren, Ling Jiao, Sha-Sha Wu, Da-Chao Mou, Zhi-Yong Miao
Summary: This study induced a novel T cell subset called Th-GM cells in a mouse CHS model and found that they were mainly expanded at the site of injury and draining lymph nodes. This method can be used to further investigate the biology of Th-GM cells and explore therapeutic strategies centered on GM-CSF in various conditions.
JOVE-JOURNAL OF VISUALIZED EXPERIMENTS
(2022)
Article
Medicine, Research & Experimental
Can M. Sungur, Qiankun Wang, Ayse N. Ozanturk, Hongbo Gao, Aaron J. Schmitz, Marina Cella, Wayne M. Yokoyama, Liang Shan
Summary: The role of NK cells in HIV-1 infections was investigated using a humanized mouse model. The study showed that NK cells directly provided anti-HIV-1 responses in nonlymphoid organs, but had limited functionality in lymphoid organs. Antiretroviral therapy and a broadly neutralizing antibody, PGT121, were found to enhance NK cell function and reduce viral load.
JOURNAL OF CLINICAL INVESTIGATION
(2022)
Article
Immunology
Yawei Liu, Robert Bockermann, Mahdieh Hadi, Iman Safari, Belinda Carrion, Marie Kveiborg, Shohreh Issazadeh-Navikas
Summary: ADAM12 is identified as a costimulatory molecule in T cells that mimics CD28 signaling to activate and induce proliferation of Th1 cells. Lack of genomic ADAM12 in T cells diminishes T-bet and IFN gamma production in Th1 cells, providing a potential target for the treatment of Th1-mediated diseases.
CELLULAR & MOLECULAR IMMUNOLOGY
(2021)
Article
Immunology
Kazutaka Terahara, Ryutaro Iwabuchi, Rieko Iwaki, Yoshimasa Takahashi, Yasuko Tsunetsugu-Yokota
Summary: Various types of non-apoptotic CD4 T-cell death, such as pyroptosis and necroptosis, are induced during the early phase of HIV infection in vivo, indicating a complex mechanism of CD4 T-cell depletion.
MICROBES AND INFECTION
(2021)
Review
Virology
Kazutaka Terahara, Ryutaro Iwabuchi, Yasuko Tsunetsugu-Yokota
Summary: Humanized mice, reconstituted with human hematopoietic stem cells or fetal thymus and HSCs, are important animal models for studying HIV-1 infection. They have limitations such as incomplete immune responses and poor distribution of human cells to secondary lymphoid tissues. Careful experimental design and utilization of technologies are needed to address these limitations and maximize the potential contributions of humanized mouse models for HIV research.
Article
Immunology
Ryutaro Iwabuchi, Keigo Ide, Kazutaka Terahara, Ryota Wagatsuma, Rieko Iwaki, Hiroko Matsunaga, Yasuko Tsunetsugu-Yokota, Haruko Takeyama, Yoshimasa Takahashi
Summary: The study reveals that CD14(+)CD1c(+) cells in humanized mouse models are phenotypically distinct from cDC2s, indicating their identity as a subset equivalent to DC3s.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Immunology
Saya Moriyama, Yu Adachi, Takashi Sato, Keisuke Tonouchi, Lin Sun, Shuetsu Fukushi, Souichi Yamada, Hitomi Kinoshita, Kiyoko Nojima, Takayuki Kanno, Minoru Tobiume, Keita Ishijima, Yudai Kuroda, Eun-Sil Park, Taishi Onodera, Takayuki Matsumura, Tomohiro Takano, Kazutaka Terahara, Masanori Isogawa, Ayae Nishiyama, Ai Kawana-Tachikawa, Masaharu Shinkai, Natsuo Tachikawa, Shigeki Nakamura, Takahiro Okai, Kazu Okuma, Tetsuro Matano, Tsuguto Fujimoto, Ken Maeda, Makoto Ohnishi, Takaji Wakita, Tadaki Suzuki, Yoshimasa Takahashi
Summary: Antibody titers against SARS-CoV-2 decrease over time, but the neutralizing potency against the original virus and variants actually improves with time. Late convalescent antibodies show increased neutralization potency against variants, suggesting that antibody response maturation enhances cross-neutralizing ability against circulating variants. This indicates that declining antibody titers may not necessarily mean declining protection.
Article
Virology
Shoji Miki, Yohei Kawai, Kaori Nakayama-Hosoya, Ryutaro Iwabuchi, Kazutaka Terahara, Yasuko Tsunetsugu-Yokota, Michiko Koga, Tetsuro Matano, Shin Kaneko, Ai Kawana-Tachikawa
Summary: The study demonstrates that HIV-specific iPSC-CTL can sustainably suppress viral replication, with longer duration compared to parental CTL clone, indicating a potential new approach for clearing the HIV reservoir.
JOURNAL OF VIROLOGY
(2022)
Article
Immunology
Ryutaro Kotaki, Yu Adachi, Saya Moriyama, Taishi Onodera, Shuetsu Fukushi, Takaki Nagakura, Keisuke Tonouchi, Kazutaka Terahara, Lin Sun, Tomohiro Takano, Ayae Nishiyama, Masaharu Shinkai, Kunihiro Oba, Fukumi Nakamura-Uchiyama, Hidefumi Shimizu, Tadaki Suzuki, Takayuki Matsumura, Masanori Isogawa, Yoshimasa Takahashi
Summary: Multiple SARS-CoV-2 variants, particularly Beta and Omicron, have the potential to evade neutralizing antibodies, even in those who have received two doses of the BNT162b2 mRNA vaccine. However, boosting with a third vaccine dose or breakthrough infection can improve the overall breadth of neutralizing antibodies. This study longitudinally profiles the cellular composition of RBD-binding memory B cell subsets and their antibody binding and neutralizing activity after the second dose of mRNA vaccine. It finds that two doses of mRNA vaccine induce an expanded antibody breadth over time, while a subset of resting memory B cells show the ability to produce Beta and Omicron-neutralizing antibodies.
SCIENCE IMMUNOLOGY
(2022)
Article
Biotechnology & Applied Microbiology
Hiroshi Ishii, Kazutaka Terahara, Takushi Nomura, Midori Okazaki, Hiroyuki Yamamoto, Tsugumine Shu, Hiromi Sakawaki, Tomoyuki Miura, David I. Watkins, Tetsuro Matano
Summary: This study demonstrates that inducing virus-specific CD8(+) T cells rather than CD4(+) T cells through specific immunogen design can enhance the protective efficacy of HIV vaccines.
Article
Microbiology
Kazutaka Terahara, Tian-Cheng Li, Keiji Matsubayashi, Hidekatsu Sakata, Takanobu Kato, Atsushi Naganuma, Koji Ogawa, Koichi Honda, Jun Itakura, Noriyuki Akutsu, Hiroshi Tobita, Masaaki Korenaga, Tatsuya Kanto, Ryuichi Sugiyama, Ryosuke Suzuki, Isao Hamaguchi, Masanori Isogawa, Yoshimasa Takahashi
Summary: This study aimed to calibrate HEV serological assays and found that the in-house ELISA had higher sensitivity for detecting HEV IgM and IgA compared to commercial kits. The performance of commercial kits could be improved by optimizing the cutoff and reducing nonspecific background noise. Asymptomatic specimens and background subtraction play important roles in the optimization of HEV serological assays.
MICROBIOLOGY SPECTRUM
(2022)
Article
Multidisciplinary Sciences
Kazutaka Terahara, Takashi Sato, Yu Adachi, Keisuke Tonouchi, Taishi Onodera, Saya Moriyama, Lin Sun, Tomohiro Takano, Ayae Nishiyama, Ai Kawana-Tachikawa, Tetsuro Matano, Takayuki Matsumura, Masaharu Shinkai, Masanori Isogawa, Yoshimasa Takahashi
Summary: The determinants of memory T cell longevity following SARS-CoV-2 infection are still unknown. This study found that the half-lives of CD4(+) and CD8(+) T cells were longer than antibody titers. Th17-like subset of CD4(+) T cells showed the longest half-life, indicating its close association with T cell longevity. In contrast, Th2 and Tfh-like T cells were more closely correlated with antibody levels.
Article
Virology
Clara Duran-Castells, Anuska Llano, Ai Kawana-Tachikawa, Anna Prats, Ignacio Martinez-Zalacain, Mie Kobayashi-Ishihara, Bruna Oriol-Tordera, Ruth Pena, Cristina Galvez, Sandra Silva-Arrieta, Bonaventura Clotet, Eva Riveira-Munoz, Esther Ballana, Julia. G. Prado, Javier Martinez-Picado, Jorge Sanchez, Beatriz Mothe, Dennis Hartigan-O'Connor, Tony Wyss-Coray, Andreas Meyerhans, Magnus Gisslen, Richard. W. Price, Carles Soriano-Mas, Jose Antonio Munoz-Moreno, Christian Brander, Marta Ruiz-Riol
Summary: High levels of SIRT2 are associated with uncontrolled HIV infection, plasma viral load, and proviral levels. SIRT2 levels are also linked to markers of neurological damage and brain involution, especially in individuals who initiate cART later. Inhibition of SIRT2 could potentially be a therapeutic target for HIV infections and their associated neurological dysfunction.
JOURNAL OF VIROLOGY
(2023)
Article
Infectious Diseases
Ni Made Mertaniasih, Soedarsono Soedarsono, Tiffany Tiara Pakasi, Zakiyathun Nuha, Manabu Ato
Summary: This research aims to investigate the impact of TB-SARS-CoV-2 co-infection and propose a conceptual strategy for an integrated management system. The system includes early detection and synchronization of TB-COVID-19 health services, providing important insights for future strategies.
TROPICAL MEDICINE AND INFECTIOUS DISEASE
(2022)
Article
Cell Biology
Eva Domenjo-Vila, Valentina Casella, Ryutaro Iwabuchi, Even Fossum, Mireia Pedragosa, Quim Castellvi, Paula Cebollada Rica, Tsuneyasu Kaisho, Kazutaka Terahara, Gennady Bocharov, Jordi Argilaguet, Andreas Meyerhans
Summary: The contribution of XCR1+ dendritic cells (DCs) and SIRPa+ DCs in maintaining T cell function during exhaustion and immunotherapeutic interventions of chronic infections is poorly understood. In a mouse model of chronic LCMV infection, XCR1+ DCs were found to be more resistant to infection and highly activated compared to SIRPa+ DCs. Exploiting XCR1+ DCs through expansion or vaccination improved CD8+ T cell functionality and virus control. PD-L1 blockade was found to be more effective when combined with increased frequency of XCR1+ DCs, enhancing the functionality of exhausted CD8+ T cell subsets.
Article
Biology
Mie Kobayashi-Ishihara, Katarina Frazao Smutna, Florencia E. Alonso, Jordi Argilaguet, Anna Esteve-Codina, Kerstin Geiger, Meritxell Genesca, Judith Grau-Exposito, Clara Duran-Castells, Selina Rogenmoser, Rene Boettcher, Jennifer Jungfleisch, Baldomero Oliva, Javier P. Martinez, Manqing Li, Michael David, Makoto Yamagishi, Marta Ruiz-Riol, Christian Brander, Yasuko Tsunetsugu-Yokota, Maria J. Buzon, Juana Diez, Andreas Meyerhans
Summary: In cell lines and HIV-1 patient PBMCs, the Schlafen 12 protein (SLFN12) is shown to be an HIV-1 restriction factor that inhibits HIV-1 replication and virus reactivation. SLFN12 establishes a post-transcriptional block in HIV-1-infected cells, dependent on the HIV-1 codon usage and its RNase active sites. SLFN12 expression in PBMCs of HIV-1-infected individuals correlates with viral loads.
COMMUNICATIONS BIOLOGY
(2023)
Article
Cell Biology
Tomohiro Takano, Miwa Morikawa, Yu Adachi, Kiyomi Kabasawa, Nicolas Sax, Saya Moriyama, Lin Sun, Masanori Isogawa, Ayae Nishiyama, Taishi Onodera, Kazutaka Terahara, Keisuke Tonouchi, Masashi Nishimura, Kentaro Tomii, Kazuo Yamashita, Takayuki Matsumura, Masaharu Shinkai, Yoshimasa Takahashi
Summary: By applying high-dimensional immune profiling, the study identified vaccine-induced immune dynamics that correlate with neutralizing antibody levels, adverse event severity, or both. Natural killer cells, dendritic cell subsets, and NKT-like cells were found to play important roles in these immune dynamics.
CELL REPORTS MEDICINE
(2022)
Article
Immunology
Tomohiro Takano, Takayuki Matsumura, Yu Adachi, Kazutaka Terahara, Saya Moriyama, Taishi Onodera, Ayae Nishiyama, Ai Kawana-Tachikawa, Shoji Miki, Kaori Hosoya-Nakayama, Midori Nakamura-Hoshi, Sayuri Seki, Natsuo Tachikawa, Yukihiro Yoshimura, Nobuyuki Miyata, Hiroshi Horiuchi, Hiroaki Sasaki, Kazuhito Miyazaki, Noriko Kinoshita, Tsutomu Sudo, Yutaro Akiyama, Rubuna Sato, Tadaki Suzuki, Tetsuro Matano, Yoshimasa Takahashi
Summary: An expanded myeloid cell compartment is a key feature of severe COVID-19, with polymorphonuclear (PMN)-MDSCs selectively expanding in survivors of severe cases in Japan, positively correlating with IL-8 levels. This transient expansion of PMN-MDSC subset could serve as a predictor of prognosis in severe COVID-19 cases.
INTERNATIONAL IMMUNOLOGY
(2021)