Article
Cell Biology
Pedro M. Rodrigues, Laura G. Sousa, Chiara Perrod, Ana R. Maceiras, Pedro Ferreirinha, Rita Pombinho, Gema Romera-Cardenas, Maria Gomez-Lazaro, Meryem Senkara, Jelena Pistolic, Didier Cabanes, Ludger Klein, Paul Saftig, Nuno L. Alves
Summary: Thymic epithelial cells (TECs) are crucial for T cell development. This study reveals that lysosomal-associated membrane protein 2 (LAMP2) is highly expressed in cortical TECs (cTECs) and plays a role in autophagy and lysosomal processes. Genetic inactivation of Lamp2 in cTECs impairs the development of CD4 T cells without directing MHC II-restricted cells into the CD8 lineage. The findings suggest that LAMP2 is important for the generation of selecting self-peptides:MHC II complexes in cTECs.
Article
Biology
Soeun Kim, Guk-Yeol Park, Jong Seok Park, Jiho Park, Hyebeen Hong, Yoontae Lee
Summary: The transcriptional repressor Capicua (CIC) plays a critical role in controlling thymic selection process, impacting both positive and negative selection of thymocytes. CIC deficiency attenuates TCR signaling in DP cells and regulates multiple genes involved in T cell development, suggesting it serves as a safeguard against autoimmunity.
Article
Biochemistry & Molecular Biology
Matthias Kaestle, Camilla Merten, Roland Hartig, Carlos Plaza-Sirvent, Ingo Schmitz, Ursula Bommhardt, Burkhart Schraven, Luca Simeoni
Summary: Lck plays a crucial role in TCR signaling and has been found to have a novel function downstream, regulating thymocyte differentiation and selection.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Immunology
Holger Winkels, Yanal Ghosheh, Kouji Kobiyama, William B. Kiosses, Marco Orecchioni, Erik Ehinger, Vasantika Suryawanshi, Sara Herrera-De la Mata, Paola Marchovecchio, Thomas Riffelmacher, Nicolas Thiault, Mitchell Kronenberg, Dennis Wolf, Gregory Seumois, Pandurangan Vijayanand, Klaus Ley
Summary: An unexpected population of CD4(+) and CD8 alpha beta(+) immune cells was discovered in healthy and atherosclerotic mice, similar to thymic DPs. These cells were found in thymus, mediastinal adipose tissue, and aortic adventitia, with differences in transcriptional profiles between locations. The extrathymic DPs may play a role in aortic vascular homeostasis and their migration appears to be locally confined.
JOURNAL OF IMMUNOLOGY
(2021)
Article
Multidisciplinary Sciences
Delong Feng, Yanhong Chen, Ranran Dai, Shasha Bian, Wei Xue, Yongchang Zhu, Zhaoqiang Li, Yiting Yang, Yan Zhang, Jiarui Zhang, Jie Bai, Litao Qin, Yoshinori Kohwi, Weili Shi, Terumi Kohwi-Shigematsu, Jing Ma, Shixiu Liao, Bingtao Hao
Summary: In this study, the authors demonstrate that the loss of Satb1 leads to changes in the identity of DP thymocytes, which is mediated by the regulation of super-enhancers through 3D genome architecture. This finding provides valuable insights into the understanding of T cell development.
NATURE COMMUNICATIONS
(2022)
Article
Multidisciplinary Sciences
Charlotte A. James, Yuexin Xu, Melissa S. Aguilar, Lichen Jing, Erik D. Layton, Martine Gilleron, Adriaan J. Minnaard, Thomas J. Scriba, Cheryl L. Day, Edus H. Warren, David M. Koelle, Chetan Seshadri
Summary: This study reveals the importance of CD4 and CD8 co-receptors in recognizing mycobacterial glycolipid antigens. The expression of either CD4 or CD8 increases the avidity of T cell receptors for mycolipids, leading to a higher intensity of fluorescence and decreased secretion threshold for interferon-gamma. Furthermore, CD8+ T cells show greater cytotoxicity compared to CD4+ T cells in individuals with active tuberculosis.
NATURE COMMUNICATIONS
(2022)
Article
Gastroenterology & Hepatology
Changying Li, Xiaonan Du, Zongshan Shen, Yunxiong Wei, Yaning Wang, Xiaotong Han, Hua Jin, Chunpan Zhang, Mengyi Li, Zhongtao Zhang, Songlin Wang, Dong Zhang, Guangyong Sun
Summary: During NAFLD progression, TCR gamma delta+ DNT cells enhance IL17A secretion and aggravate liver inflammation, whereas TCR alpha beta(+) DNT cells decrease GZMB production and lead to weakened immunoregulatory function. Shifting of balance from TCR gamma delta+ DNT cell response to one that favors TCR alpha beta(+) DNT regulation would be beneficial for the prevention and treatment of NAFLD.
CELLULAR AND MOLECULAR GASTROENTEROLOGY AND HEPATOLOGY
(2022)
Article
Multidisciplinary Sciences
Joseph S. Dolina, Joey Lee, Eugene L. Moore, Jennifer L. Hope, Donald T. Gracias, Takaji Matsutani, Ashu Chawla, Jason A. Greenbaum, Joel Linden, Stephen P. Schoenberger
Summary: During acute infection, CD4(+) regulatory T cells play a crucial role in regulating the immune response by suppressing cytotoxic CD8(+) T lymphocytes through different mechanisms. Early T cells inhibit primary CTL expansion through adenosine production, while late-phase T-regs suppress T cell proliferation through the transfer of cAMP. This study reveals the distinct roles of different T-reg lineages in fine-tuning CTL priming and contraction phases during acute infection.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Immunology
Hao H. Yiu, Louis N. Schoettle, Marlene Garcia-Neuer, Joseph N. Blattman, Philip L. F. Johnson
Summary: This passage discusses the diversity generation of T-cell receptors in the adaptive immune system and the differences among various receptor types, focusing on the presence of public receptor sequences in different contexts and the factors influencing their abundance. Thymic or peripheral selection is identified as a significant factor in increasing the abundances of public TCR sequences.
Article
Immunology
J. Luke Postoak, Wenqiang Song, Guan Yang, Xingyi Guo, Shiyun Xiao, Cherie E. Saffold, Jianhua Zhang, Sebastian Joyce, Nancy R. Manley, Lan Wu, Luc Van Kaer
Summary: This study reveals the important role of lipid kinase Vps34 in the development and selection of CD4 T cells during antigen processing and presentation.
JOURNAL OF EXPERIMENTAL MEDICINE
(2022)
Article
Multidisciplinary Sciences
Kimberly G. Laffey, Robert J. Stiles, Melissa J. Ludescher, Tessa R. Davis, Shariq S. Khwaja, Richard J. Bram, Peter J. Wettstein, Venkataraman Ramachandran, Christopher A. Parks, Edwin E. Reyes, Alejandro Ferrer, Jenna M. Canfield, Cory E. Johnson, Richard D. Hammer, Diana Gil, Adam G. Schrum
Summary: During normal T cell development, a low-frequency population of early all TCR+ DN cells is present, which requires CD3δ for their generation/detection. These cells can respond to MHC and display coreceptor-independent MHC reactivity. It has been observed that these cells are susceptible to T-ALL transformation.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Immunology
Laura B. Chopp, Xiaoliang Zhu, Yayi Gao, Jia Nie, Jatinder Singh, Parimal Kumar, Kelly Z. Young, Shil Patel, Caiyi Li, Mariah Balmaceno-Criss, Melanie S. Vacchio, Michael M. Wang, Ferenc Livak, Juanita L. Merchant, Lie Wang, Michael C. Kelly, Jinfang Zhu, Remy Bosselut
Summary: The transcription factors Zfp281 and Zfp148 play important roles in initiating CD4(+) lineage gene expression and regulating cytokine expression by T(H)2 effector cells. They promote the differentiation of CD4(+) T cells in the thymus and enhance T(H)2 cytokine expression in peripheral T cells, but do not affect the expression of the T(H)2 lineage-determining transcription factor Gata3.
SCIENCE IMMUNOLOGY
(2023)
Article
Oncology
Ze Zhang, Rondi Butler, Devin C. Koestler, Shelby Bell-Glenn, Gayathri Warrier, Annette M. Molinaro, Brock C. Christensen, John K. Wiencke, Karl T. Kelsey, Lucas A. Salas
Summary: This study reveals shared epigenetic regulation during memory cell differentiation in immune cell lineages. Distinct DNA methylation changes were observed in different cell lineages during central to effector memory differentiation. Additionally, unique DNA methylation patterns were found in terminally differentiated effector memory cells.
CLINICAL EPIGENETICS
(2022)
Article
Biochemistry & Molecular Biology
Seeyoung Choi, Jan Lee, Teri Hatzihristidis, Guillaume Gaud, Avik Dutta, Awadhesh Arya, Lauren M. Clubb, Daniel B. Stamos, Adrienn Markovics, Katalin Mikecz, Paul E. Love
Summary: THEMIS is a critical protein in T cell development at the positive selection stage. It enhances the activity of the tyrosine phosphatase SHP1 to dampen T cell antigen receptor signaling and prevent inappropriate negative selection. It also promotes positive selection by enhancing the sensitivity of CD4+CD8+ thymocytes to low-affinity ligands.
Article
Multidisciplinary Sciences
Elena R. Bovolenta, Eva M. Garcia-Cuesta, Lydia Horndler, Julia Ponomarenko, Wolfgang W. Schamel, Mario Mellado, Mario Castro, David Abia, Hisse M. van Santen
Summary: Signaling through T cell receptor (TCR) plays a critical role in the development, maintenance, and activation of T cells. This study reveals that the strength of pre-TCR-mediated signaling during T cell development determines the diversity of TCR beta repertoire for positive and negative selection.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Cell Biology
Charles Sinclair, Masahiro Ono, Benedict Seddon
IMMUNOLOGY AND CELL BIOLOGY
(2015)
Editorial Material
Immunology
Benedict Seddon
Article
Multidisciplinary Sciences
Thea Hogan, Graeme Gossel, Andrew J. Yates, Benedict Seddon
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2015)
Article
Immunology
Louise V. Webb, Steven C. Ley, Benedict Seddon
JOURNAL OF EXPERIMENTAL MEDICINE
(2016)
Article
Biology
Graeme Gossel, Thea Hogan, Daniel Cownden, Benedict Seddon, Andrew J. Yates
Article
Immunology
Jie Yang, Ferry Cornelissen, Natalie Papazian, Rogier M. Reijmers, Miriam Llorian, Tom Cupedo, Mark Coles, Benedict Seddon
JOURNAL OF EXPERIMENTAL MEDICINE
(2018)
Article
Biochemistry & Molecular Biology
Sanket Rane, Thea Hogan, Benedict Seddon, Andrew J. Yates
Review
Immunology
Benedict Seddon, Andrew J. Yates
IMMUNOLOGICAL REVIEWS
(2018)
Article
Immunology
Louise Webb, Alessandro Barbarulo, Jelle Huysentruyt, Tom Vanden Berghe, Nozomi Takahashi, Steven Ley, Peter Vandenabeele, Benedict Seddon
Review
Immunology
Joao T. Barata, Scott K. Durum, Benedict Seddon
Article
Biology
Thea Hogan, Maria Nowicka, Daniel Cownden, Claire F. Pearson, Andrew J. Yates, Benedict Seddon
Biographical-Item
Immunology
Benedict Seddon, Fiona Powrie, Neil Barclay
Article
Biology
Sanket Rane, Thea Hogan, Edward Lee, Benedict Seddon, Andrew J. Yates
Summary: In this study, a unified model of naive CD4 and CD8 T cell population dynamics in mice was identified using multiple modelling and experimental approaches. It was found that both subsets divide rarely and progressively increase their survival capacity with cell age. Newly generated naive CD8 T cells were found to be lost more rapidly during the first 3-4 weeks of life. No evidence for elevated division rates in neonates or feedback regulation of naive T cell numbers at any age was found.
Article
Biology
Thea Hogan, Andrew Yates, Benedict Seddon