Article
Immunology
Matthew D. D. Taves, Kaitlynn M. M. Donahue, Jing Bian, Margaret C. C. Cam, Jonathan D. D. Ashwell
Summary: TECs produce glucocorticoids to promote T cell repertoire, and the expression of Cyp11b1, an enzyme involved in glucocorticoid production, is dependent on Aire. Aire not only induces tissue-restricted antigen expression, but also promotes glucocorticoid production, expanding and enhancing the T cell receptor repertoire.
SCIENCE IMMUNOLOGY
(2023)
Article
Multidisciplinary Sciences
Jason A. Carter, Leonie Stroemich, Matthew Peacey, Sarah R. Chapin, Lars Velten, Lars M. Steinmetz, Benedikt Brors, Sheena Pinto, Hannah Meyer
Summary: This study reveals the transcriptomic diversity of mTECs in the thymus and establishes a web portal for querying their transcriptome, which may aid in identifying the drivers of autoimmune diseases.
NATURE COMMUNICATIONS
(2022)
Article
Oncology
Minoru Matsumoto, Takuya Ohmura, Yuto Hanibuchi, Mayuko Ichimura-Shimizu, Yasuyo Saijo, Hirohisa Ogawa, Ryuichiro Miyazawa, Junko Morimoto, Koichi Tsuneyama, Mitsuru Matsumoto, Takeshi Oya
Summary: Despite the physiological distinction between cTECs and mTECs, the origin of TCs and other thymic epithelial tumors has been unclear. By studying the mTEC-specific transcriptional regulator AIRE, it was found that a significant proportion of TCs express AIRE with characteristic nuclear dot morphology. This expression was supported by RNA-seq data and further analysis revealed that TCs exhibit molecular characteristics of multiple mTEC subpopulations, suggesting their derivation from mTECs.
Article
Biochemistry & Molecular Biology
Meng Zhao, Ariel Quintana, Chen Zhang, Alexander Y. Andreyev, William Kiosses, Tomomi Kuwana, Anne Murphy, Patrick G. Hogan, Mitchell Kronenberg
Summary: The differentiation of NKT2 cells requires higher and sustained calcium signals compared to their NKT1 counterparts, which is connected with mitochondria and cellular metabolism.
Article
Immunology
Duan Ni, Jian Tan, Remy Robert, Jemma Taitz, Anjie Ge, Camille Potier-Villette, Julen Gabirel Araneta Reyes, Alanna Spiteri, Claire Wishart, Charles Mackay, Laura Piccio, Nicholas Jonathan Cole King, Laurence Macia
Summary: This study reveals a new role for GPR109A in thymic Treg development. Gpr109a-/- mice have increased Treg under basal conditions in multiple organs. GPR109A is expressed on medullary thymic epithelial cells (mTECs) and its absence leads to increased autoimmune regulator expression and enhanced mTEC functionality.
EUROPEAN JOURNAL OF IMMUNOLOGY
(2023)
Article
Biology
Noella Lopes, Nicolas Boucherit, Jeremy C. Santamaria, Nathan Provin, Jonathan Charaix, Pierre Ferrier, Matthieu Giraud, Magali Irla
Summary: Interactions between developing T cells and Aire(+) medullary thymic epithelial cells are crucial for central tolerance induction in the thymus. Self-reactive CD4(+) thymocytes control the transcriptional regulators and composition of mTEC(lo) subsets, including Aire(+) mTEC(hi) precursors, post-Aire and tuft-like mTECs. These interactions upregulate the expression of tissue-restricted self-antigens, cytokines, chemokines, and adhesion molecules important for T-cell development. Our study reveals that self-reactive CD4(+) thymocytes control multiple facets of immature mTECs, determining their heterogeneity.
Article
Multidisciplinary Sciences
Fabian Klein, Clara Veiga-Villauriz, Anastasiya Borsch, Stefano Maio, Sam Palmer, Fatima Dhalla, Adam E. E. Handel, Saulius Zuklys, Irene Calvo-Asensio, Lucas Musette, Mary E. E. Deadman, Andrea J. J. White, Beth Lucas, Graham Anderson, Georg A. A. Hollander
Summary: The network of thymic stromal cells plays a crucial role in T cell development and selection. By employing advanced techniques such as flow cytometry and machine learning, the researchers identified novel subpopulations of thymic epithelial cells and characterized their functions, particularly in perinatal cortical TEC.
NATURE COMMUNICATIONS
(2023)
Article
Cell Biology
Xie Xu, Kai He, Robert D. Hoffman, Yuyuan Ying, Nana Tao, Wenqin Guo, Jiaman Shen, Xi Liu, Meiya Li, Meiqiu Yan, Guiyuan Lv, Jianli Gao
Summary: In this study, the impact of T beta 15 on thymic epithelial cells (TECs) was investigated. It was found that T beta 15 can affect the spatial development of TECs, T cell differentiation, and thymic output. T beta 15 OX inhibits the migration of TECs to the medulla and blocks the positive selection of thymocytes. Knockdown of T beta 15 accelerates TEC differentiation. These findings provide important insights into the development and degeneration of the thymus.
Article
Multidisciplinary Sciences
Yoshiaki Yasumizu, Naganari Ohkura, Hisashi Murata, Makoto Kinoshita, Soichiro Funaki, Satoshi Nojima, Kansuke Kido, Masaharu Kohara, Daisuke Motooka, Daisuke Okuzaki, Shuji Suganami, Eriko Takeuchi, Yamami Nakamura, Yusuke Takeshima, Masaya Arai, Satoru Tada, Meinoshin Okumura, Eiichi Morii, Yasushi Shintani, Shimon Sakaguchi, Tatsusada Okuno, Hideki Mochizuki
Summary: This study reveals the ectopic expression of neuromuscular molecules in MG-type thymoma, specifically in a distinct subpopulation of medullary thymic epithelial cells (nmTECs). MG-thymoma exhibits microenvironments dedicated to autoantibody production and cell-cell interactions between nmTECs and T/B cells. The findings suggest that nmTECs play a significant role in the pathogenesis of MG through ectopic expression of neuromuscular molecules.
NATURE COMMUNICATIONS
(2022)
Article
Immunology
Xue Dong, Jiayu Zhang, Qian Zhang, Zhanfeng Liang, Yanan Xu, Yong Zhao, Baojun Zhang
Summary: Thymic epithelial cells (TECs) play a critical role in the development and function of the immune system. This study demonstrates the importance of Dhx9 protein in the differentiation and function of mTECs, and its deficiency leads to decreased TEC cell numbers and the development of spontaneous autoimmune disorders.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Multidisciplinary Sciences
Thomas Barthlott, Adam E. Handel, Hong Ying Teh, Rushika C. Wirasinha, Katrin Hafen, Saulius Zuklys, Benoit Roch, Stuart H. Orkin, Jean-Pierre de Villartay, Stephen R. Daley, Georg A. Hollaender
Summary: Thymic T cell development and T cell receptor repertoire selection rely on molecular signals from thymic epithelial cells (TEC), whose development and function are epigenetically regulated. Disruption of PRC2 activity alters H3K27me3 configuration, impairs TEC functions, and affects T cell development.
NATURE COMMUNICATIONS
(2021)
Article
Immunology
Jiayi Dong, Lindsey M. Warner, Ling-Li Lin, Mei-Chi Chen, Ryan M. O'Connell, Li-Fan Lu
Summary: miR-155 plays a crucial role in promoting tT reg cell differentiation by promoting mTEC maturation in the thymus. RANKL stimulation induces miR-155 expression to target molecules within the TGF beta signaling pathway, safeguarding thymic medulla integrity.
JOURNAL OF EXPERIMENTAL MEDICINE
(2021)
Article
Biochemistry & Molecular Biology
Catarina S. Silva, Mariana T. Cerqueira, Rui L. Reis, Albino Martins, Nuno M. Neves
Summary: The presence of laminin-2 positively affects the cell viability and proliferation of cTECs, while the density of laminin-2 influences the expression of cTECs genes. Higher concentrations of laminin-2 lead to an increased percentage of adherent CD4-CD8- thymocytes and a decreased percentage of CD4+CD8+ thymocytes.
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
(2022)
Review
Biochemistry & Molecular Biology
Alexia Borelli, Magali Irla
Summary: The LT alpha 1 beta 2/LT beta R signaling axis plays a pivotal role in regulating thymic function, including the generation of a diverse and self-tolerant T-cell repertoire, the migration of thymocytes, and the differentiation of medullary thymic epithelial cells. This axis also contributes to the recovery of thymic function after myeloablative conditioning, offering potential in regenerative medicine.
CELL DEATH AND DIFFERENTIATION
(2021)
Review
Biochemistry & Molecular Biology
Christos Masaoutis, Kostas Palamaris, Stefania Kokkali, Georgia Levidou, Stamatios Theocharis
Summary: Thymic Epithelial Tumors (TETs) are rare tumors originating from the epithelial component of the thymus gland and characterized by a heterogenous immune cellular composition. The tumor microenvironment plays a crucial role in the immune response of TETs and can be targeted by immune checkpoint inhibitors (ICIs). Clinical trials have demonstrated the efficacy of PD-L1 inhibitors in specific subtypes of TETs, although further studies with larger sample sizes are needed for more reliable conclusions.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Editorial Material
Primary Health Care
Lauren M. Quinn, Rajeeb Rashid, Parth Narendran, David Shukla
BRITISH JOURNAL OF GENERAL PRACTICE
(2023)
Letter
Endocrinology & Metabolism
Hood Thabit, Charlotte Boughton, Womba Mubita, Jose Rubio, Julia K. Mader, Parth Narendran, Mark Evans, Lalantha Leelarathna, Malgorzata E. Wilinska, Catherine Fullwood, Alice M. Gregory, Roman Hovorka, Martin K. Rutter
DIABETES OBESITY & METABOLISM
(2023)
Review
Endocrinology & Metabolism
Ian Litchfield, Timothy Barrett, Julian P. Hamilton-Shield, T. H. M. Moore, Parth Narendran, Sabi Redwood, Aidan Searle, Suma Uday, Jess Wheeler, Sheila Greenfield
Summary: Self-management support programmes have become important in the treatment of chronic diseases, including diabetes. However, the promised impact on glycated haemoglobin (HbA(1c)) and self-management behaviours for children and young people with diabetes remains unachieved, calling for an evaluation of current thinking and evidence to develop better targeted programmes for this age group.
Article
Endocrinology & Metabolism
Benjamin C. T. Field, Yue A. Ruan, Kinga Varnai, Jim Davies, Robert E. J. Ryder, Rajiv Gandhi, Sophie Harris, Dinesh Nagi, Dipesh Patel, Punith H. Kempegowda, Sarah G. Wild, Emma Wilmot, Kamlesh Khunti, Rustam Rea, Parth Narendran
Summary: This study investigated the characteristics of people hospitalized with COVID-19 and diabetic ketoacidosis (DKA) or hyperosmolar hyperglycaemic state (HHS), and identified risk factors for mortality and intensive care admission. The study found that DKA had a higher mortality rate and a lower proportion of non-White ethnicity compared to HHS. Previous insulin therapy was strongly associated with survival in type 2 diabetes-associated DKA.
DIABETES OBESITY & METABOLISM
(2023)
Editorial Material
Endocrinology & Metabolism
Lauren M. Quinn, Rabbi Swaby, Danijela Tatovic, Parth Narendran, Rachel E. J. Besser, Colin M. Dayan
DIABETES OBESITY & METABOLISM
(2023)
Article
Endocrinology & Metabolism
Lauren M. Quinn, Parth Narendran, Matthew J. Randell, Kirandeep Bhavra, Felicity Boardman, Sheila M. Greenfield, Ian Litchfield
Summary: This study explores the views of stakeholders towards paediatric general population screening for type 1 diabetes in the UK. The benefits of screening include education, monitoring, and helping families prepare for a future with type 1 diabetes. However, there are concerns about lack of evidence for public acceptability and potential harms. Overall, stakeholders believe that the current harms outweigh the benefits, but this view may change if prevention therapies become available.
Article
Immunology
Kieran D. James, Andrea J. White, William E. Jenkinson, Graham Anderson
Summary: Gamma delta T-cell development and effector priming in adulthood are controlled by the medulla, with the medullary epithelial product CCL21 playing a crucial role in this process.
EUROPEAN JOURNAL OF IMMUNOLOGY
(2023)
Article
Multidisciplinary Sciences
Beth Lucas, Andrea J. White, Fabian Klein, Clara Veiga-Villauriz, Adam Handel, Andrea Bacon, Emilie J. Cosway, Kieran D. James, Sonia M. Parnell, Izumi Ohigashi, Yousuke Takahama, William E. Jenkinson, Georg A. Hollander, Wei-Yu Lu, Graham Anderson
Summary: Although the importance of thymic epithelial cells (TEC) in thymus physiology is established, the development of functionally diverse TEC populations remains incompletely understood. Here, using fate-mapping experiments in the embryonic thymus, the authors identify keratin19(+) multipotent progenitor cells that support medullary TEC diversity in adulthood.
NATURE COMMUNICATIONS
(2023)
Article
Endocrinology & Metabolism
Thomas S. J. Crabtree, Tomas P. Griffin, Yew W. Yap, Parth Narendran, Geraldine Gallen, Niall Furlong, Iain Cranston, Ali Chakera, Chris Philbey, Muhammad Ali Karamat, Sanjay Saraf, Shafie Kamaruddin, Eleanor Gurnell, Alyson Chapman, Sufyan Hussain, Jackie Elliott, Lalantha Leelarathna, Robert E. J. Ryder, Peter Hammond, Alistair Lumb, Pratik Choudharyq, Emma G. Wilmot
Summary: The study found that switching to hybrid closed-loop (HCL) insulin delivery systems led to improvements in HbA1c, time in range, hypoglycemia, and quality of life in adults with type 1 diabetes, despite previous use of intermittently scanned continuous glucose monitoring and insulin pump therapy.
Article
Endocrinology & Metabolism
Rachel A. Elliott, Gabriel Rogers, Mark L. Evans, Sankalpa Neupane, Gerry Rayman, Sarah Lumley, Iain Cranston, Parth Narendran, Christopher J. Sutton, Vicky P. Taxiarchi, Matthew Burns, Hood Thabit, Emma G. Wilmot, Lalantha Leelarathna, FLASH UK Trial Study Grp
Summary: This study aims to assess the economic impact of intermittently scanned continuous glucose monitoring (isCGM) compared with self-monitoring of blood glucose with finger pricking (SMBG). The results show that although isCGM is associated with increased short-term costs, its benefits in lowering HbA1c justify the costs in the long-term, as long as the effect lasts into the medium term.
Article
Endocrinology & Metabolism
David S. Church, Peter Barker, Keith A. Burling, Shah K. Shinwari, Carmel Kennedy, Diarmuid Smith, David P. Macfarlane, Andrew Kernohan, Anna Stears, Muhammad A. Karamat, Karen Whyte, Parth Narendran, David J. Halsall, Robert K. Semple
Summary: This study evaluated a practical biochemical approach to identify actionable anti-insulin antibodies and assessed its utility in therapeutic decision making. The results showed that anti-insulin antibodies should be considered in insulin-treated diabetes with unexplained glycaemic lability. Combining immunoassays with PEG precipitation can stratify their significance.
Article
Endocrinology & Metabolism
Lalantha Leelarathna, Christopher J. Sutton, Mark L. Evans, Sankalpa Neupane, Gerry Rayman, Sarah Lumley, Iain Cranston, Parth Narendran, Ashma Krishan, Vicky P. Taxiarchi, Katharine Barnard-Kelly, Rachel A. Elliott, Matthew Burns, Maisie Camm, Hood Thabit, Emma G. Wilmot, FLASH UK Trial Study Grp
Summary: The FLASH-UK trial demonstrated the effectiveness of intermittently scanned continuous glucose monitoring (isCGM) in reducing blood glucose levels for individuals with type 1 diabetes. The study found consistent results across various baseline characteristics.
Article
Multidisciplinary Sciences
Emilie J. Cosway, Kieran D. James, Andrea J. White, Sonia M. Parnell, Andrea Bacon, Andrew N. J. Mckenzie, W. E. Jenkinson, Graham Anderson
Summary: The study demonstrates the importance of interleukin 33 (IL-33) in thymus regeneration, showing that it stimulates the expansion of innate lymphoid cells (ILC2) and triggers the production of IL-4 by eosinophils, leading to the recovery of thymus mesenchyme.
NATURE COMMUNICATIONS
(2023)
Letter
Endocrinology & Metabolism
Hood Thabit, Charlotte Boughton, Womba Mubita, Jose Rubio, Stuart Allen, Robert Heugh, Julia K. Mader, Parth Narendran, Mark Evans, Lalantha Leelarathna, Malgorzata E. Wilinska, Catherine Fullwood, Clifford Garratt, Roman Hovorka, Martin K. Rutter
DIABETES OBESITY & METABOLISM
(2023)