Article
Immunology
Angelica W. Y. Lau, Vivian M. Turner, Katherine Bourne, Jana R. Hermes, Tyani D. Chan, Robert Brink
Summary: The BAFF/BAFFR signaling pathway is necessary for the generation of unmutated, GC-independent MBCs derived directly from activated B cells, while not affecting GC B cells or GC-derived MBCs. Both types of MBCs require input from this pathway for optimal long-term survival.
JOURNAL OF EXPERIMENTAL MEDICINE
(2021)
Article
Cell Biology
Qianqian Duan, Jiying Ding, Fangfang Li, Xiaowei Liu, Yunan Zhao, Hongxiu Yu, Yong Liu, Lianjun Zhang
Summary: This study demonstrates that SIRT5 is dispensable for the effector function and memory differentiation of CD8(+) T cells.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Article
Multidisciplinary Sciences
Sarah Adamo, Jan Michler, Yves Zurbuchen, Carlo Cervia, Patrick Taeschler, Miro E. Raeber, Simona Baghai Sain, Jakob Nilsson, Andreas E. Moor, Onur Boyman
Summary: Researchers used spectral flow cytometry combined with cellular indexing of transcriptomes and T cell receptor sequencing to longitudinally characterize individual SARS-CoV-2-specific CD8(+) T cells from patients with COVID-19, identifying a distinct signature marking long-lived memory CD8(+) T cells. The study found that SARS-CoV-2-specific memory CD8(+) T cells persisting 1 year after acute infection express specific markers and exhibit characteristics resembling effector memory T cells, and that certain transcriptional signatures and signaling pathways are associated with the fate of individual clones of these cells.
Article
Multidisciplinary Sciences
Aenne Harberts, Constantin Schmidt, Joanna Schmid, Daniel Reimers, Friedrich Koch-Nolte, Hans-Willi Mittruecker, Friederike Raczkowski
Summary: IRF4 is essential for the activation and reactivation of CD8(+) memory T cells, but does not affect their overall survival. However, the formation and maintenance of CD8(+) tissue-resident memory T cells appears to depend on IRF4.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Multidisciplinary Sciences
Amit Jairaman, Shivashankar Othy, Joseph L. Dynes, Andriy Yeromin, Angel Zavala, Milton L. Greenberg, Jamison L. Nourse, Jesse R. Holt, Stuart M. Cahalan, Francesco Marangoni, Ian Parker, Medha M. Pathak, Michael D. Cahalan
Summary: In an animal model for multiple sclerosis, mice with genetic deletion of Piezo1 in T cells showed diminished disease severity. Piezo1 was not essential for lymph node homing, T cell proliferation, or differentiation into proinflammatory T helper cells, but its deletion resulted in enhanced TGF beta signaling and an expanded pool of regulatory T cells. Deletion of Piezo1 specifically in T-reg cells led to significant attenuation of EAE.
Article
Biochemistry & Molecular Biology
Chang-Hwan Seong, Norika Chiba, Joji Kusuyama, Muhammad Subhan Amir, Nahoko Eiraku, Sachiko Yamashita, Tomokazu Ohnishi, Norifumi Nakamura, Tetsuya Matsuguchi
Summary: BMP9 induces periodic increases of Hes1 mRNA and protein expression in osteoblasts through an autocrine negative feedback mechanism, which is significantly inhibited by an ALK inhibitor and overexpression of inhibitory Smad7. The transcriptional activation of Hes1 by BMP9 in osteoblasts is dependent on two Smad-binding sites in the upstream region of the gene.
Article
Immunology
Anjun Jiao, Haiyan Liu, Renyi Ding, Huiqiang Zheng, Cangang Zhang, Zhao Feng, Lei Lei, Xin Wang, Yanhong Su, Xiaofeng Yang, Chenming Sun, Lianjun Zhang, Liang Bai, Lina Sun, Baojun Zhang
Summary: This study demonstrates the crucial role of mediator complex subunit 1 (Med1) in controlling effector CD8(+) T cell differentiation and survival during acute bacterial infection. Med1 deficiency leads to impaired expansion, reduced terminally differentiated and effector cell populations, enhanced cell apoptosis, and increased expression of inhibitory receptors. The transcriptional programs mediated by T-bet and Zeb2 are impaired in Med1-deficient CD8(+) T cells. Overexpression of T-bet can rescue the differentiation and survival of Med1-deficient CD8(+) effector T cells. Mechanistically, the transcription factor C/EBP beta promotes T-bet expression through interacting with Med1 in effector T cells.
JOURNAL OF IMMUNOLOGY
(2022)
Article
Cell Biology
Melissa G. Lechner, Zikang Zhou, Aline T. Hoang, Nicole Huang, Jessica Ortega, Lauren N. Scott, Ho -Chung Chen, Anushi Y. Patel, Rana Yakhshi-Tafti, Kristy Kim, Willy Hugo, Pouyan Famini, Alexandra Drakaki, Antoni Ribas, Trevor E. Angell, Maureen A. Su
Summary: Autoimmune toxicity is an increasing challenge in using immune checkpoint inhibitors for cancer treatment. This study investigated the immune infiltrates in ICI-thyroiditis patients and identified a dominant population of cytotoxic CD8+ T cells. The researchers also found that interleukin-21 played a crucial role in the formation of these thyrotoxic CD8+ T cells and validated the findings in a mouse model. These findings provide insights into the mechanisms and potential therapeutic targets for individuals with IRAEs.
SCIENCE TRANSLATIONAL MEDICINE
(2023)
Article
Biology
Tomonori Iyoda, Kanako Shimizu, Takaho Endo, Takashi Watanabe, Ichiro Taniuchi, Honoka Aoshima, Mikiko Satoh, Hiroshi Nakazato, Satoru Yamasaki, Shin-ichiro Fujii
Summary: This study reveals that Zeb2 plays a crucial role in the differentiation and maintenance of iNKT cells, and regulates the formation of memory iNKT cells by preventing apoptosis of Klrg1+ long-lived iNKT cells.
COMMUNICATIONS BIOLOGY
(2023)
Article
Immunology
Joy Edwards-Hicks, Petya Apostolova, Joerg M. Buescher, Hannes Maib, Michal A. Stanczak, Mauro Corrado, Ramon I. Klein I. Geltink, Maria Elena Maccari, Matteo Villa, Gustavo E. Carrizo, David E. Sanin, Francesc Baixauli, Beth Kelly, Jonathan D. Curtis, Fabian Haessler, Annette Patterson, Cameron S. Field, George Caputa, Ryan L. Kyle, Melanie Soballa, Minsun Cha, Harry Paul, Jacob Martin, Katarzyna M. Grzes, Lea Flachsmann, Michael Mitterer, Liang Zhao, Frances Winkler, David Ali Rafei-Shamsabadi, Frank Meiss, Bertram Bengsch, Robert Zeiser, Daniel J. Puleston, David O'Sullivan, Edward J. Pearce, Erika L. Pearce
Summary: The authors demonstrate the impact of metabolic alteration on the acyl chain composition on phosphoinositide-driven signaling in CD8(+) T cells. They find that naive T cells are rich in polyunsaturated phosphoinositides, while effector T cells predominantly have saturated fatty acyl chains. The different pools of phosphoinositides play distinct roles in initiating and sustaining effector function in CD8(+) T cell differentiation.
Article
Cell Biology
Anders B. Klein, Trine S. Nicolaisen, Kornelia Johann, Andreas M. Fritzen, Cecilie Mathiesen, Claudia Gil, Nanna S. Pilmark, Kristian Karstoft, Martin B. Blond, Jonas S. Quist, Randy J. Seeley, Kristine Faerch, Jens Lund, Maximilian Kleinert, Christoffer Clemmensen
Summary: Metformin has been widely used, but the mechanism of its weight loss effect is not fully understood. This study confirms that metformin can increase the levels of GDF15 in the body, but the role of the GDF15-GFRAL pathway in mediating the weight loss effect of metformin remains controversial. The results suggest that the effects of metformin on energy balance may not solely depend on the GDF15-GFRAL pathway.
Article
Immunology
Lamine Alaoui, Javiera Villar, Renaud Leclere, Simon Le Gallou, Francis Relouzat, Henri-Alexandre Michaud, Karin Tarte, Natacha Teissier, Benoit Favier, Mikael Roussel, Elodie Segura
Summary: This study characterizes the phenotype, transcriptome, life cycle, and function of human tonsil macrophages, and identifies three subtypes with distinct features. CD36(hi) macrophages are related to monocytes, CD36(lo) macrophages have features of embryonic origin, and CD36(int) macrophages display mixed characteristics. Functionally, CD36(hi) macrophages are specialized in stimulating T follicular helper cells by producing Activin A. Stromal cell-derived TNF-alpha is identified as the inducer of Activin A secretion.
JOURNAL OF EXPERIMENTAL MEDICINE
(2023)
Article
Gastroenterology & Hepatology
Christian David Schmid, Victor Olsavszky, Manuel Reinhart, Vanessa Weyer, Felix A. Trogisch, Carsten Sticht, Manuel Winkler, Sina W. Kurschner, Johannes Hoffmann, Roxana Ola, Theresa Staniczek, Joerg Heineke, Beate K. Straub, Jens Mittler, Kai Schledzewski, Peter ten Dijke, Karsten Richter, Steven Dooley, Cyrill Geraud, Sergij Goerdt, Philipp-Sebastian Koch
Summary: This study established an HHT mouse model with liver vascular malformations and investigated the role of ALK1 signaling in liver vessel formation and metabolic function. The results showed that hepatic endothelial ALK1 signaling protects from development of vascular malformations and preserves organ-specific endothelial differentiation and angiocrine signaling.
Article
Hematology
Nina Germic, Aref Hosseini, Darko Stojkov, Kevin Oberson, Meike Claus, Charaf Benarafa, Sara Calzavarini, Anne Angelillo-Scherrer, Isabelle C. Arnold, Anne Mueller, Carsten Riether, Shida Yousefi, Hans-Uwe Simon
Summary: The study demonstrates that knocking out Atg5 in eosinophils results in a decrease in mature eosinophils, an increase in immature cells, and affects cell proliferation and differentiation. Additionally, Atg5-deficient eosinophils show enhanced degranulation and bacterial killing abilities, leading to better clearance of bacterial infections in vivo models.
Article
Biochemistry & Molecular Biology
Jeremy A. O'Sullivan, Frederick J. Kohlhapp, Andrew Zloza, Lourdes Plaza-Rojas, Brianna Burke, Nickolai O. Dulin, Jose A. Guevara-Patino
Summary: After exposure to an antigen, CD8 T cells make a decision to become either short-lived effector cells (SLECs) or memory progenitor effector cells (MPECs). SLECs have immediate effector function but lower lifespan and proliferative capacity compared to MPECs. TGF beta mediates the contraction phase of CD8 T cell response after infection, selectively targeting SLECs. The study aims to investigate the factors determining TGF beta sensitivity in CD8 T cell precursor stage, and the results show that SLECs are more sensitive to TGF beta than MPECs, possibly due to differential expression of TGF beta RI and RGS3 and the binding of SLEC-related transcriptional activator T-bet to the TGF beta RI promoter.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)