Article
Medicine, Research & Experimental
Aditi Narsale, Breanna Lam, Rosa Moya, TingTing Lu, Alessandra Mandelli, Irene Gotuzzo, Benedetta Pessina, Glanmaria Giamporcaro, Rhonda Geoffrey, Kerry Buchanan, Mark Harris, Anne-Sophie Bergot, Ranjeny Thomas, Martin J. Hessner, Manuela Battaglia, Elisavet Serti, Joanna D. Davies
Summary: The study confirms the important role of CD4(+)CD25(+)CD127(hi) cells in partial remission and immunotherapy outcomes in T1D patients, showing their maintenance of an antiinflammatory environment is crucial for partial remission, 11 cell survival, and response to antiinflammatory immunotherapy.
Article
Medicine, General & Internal
Teresa Quattrin, Lucy D. Mastrandrea, Lucy S. K. Walker
Summary: Type 1 diabetes is a chronic disease caused by autoimmune destruction of pancreatic beta cells, and individuals with this disease rely on insulin for survival. Despite advancements, the burden of this disease remains high. Research shows that blocking the immune attack on beta cells holds promise in preserving endogenous insulin production.
Article
Medicine, Research & Experimental
Laura M. Jacobsen, Kirsten Diggins, Lori Blanchfield, James Mcnichols, Daniel J. Perry, Jason Brant, Xiaoru Dong, Rhonda Bacher, Vivian H. Gersuk, Desmond A. Schatz, Mark A. Atkinson, Clayton E. Mathews, Michael J. Haller, S. Alice Long, Peter S. Linsley, Todd M. Brusko
Summary: This study evaluated the immunological outcomes of high-dose anti-thymocyte globulin (ATG) treatment and found that it can preserve regulatory T cells (Tregs), with treatment response closely associated with changes in levels of cytokines such as IL-6, IP-10, and TNF-a. These findings are valuable for identifying clinical response to ATG treatment in type 1 diabetes patients.
Article
Medicine, Research & Experimental
Klaudia Ciesielska-Figlon, Agnieszka Daca, Adam Kokotkiewicz, Maria Luczkiewicz, Bozena Zabiegala, Jacek M. Witkowski, Katarzyna A. Lisowska
Summary: This study examined the immunomodulatory properties of essential oil and its constituents from Nigella sativa seeds. The results showed that the essential oil and thymoquinone inhibited lymphocyte proliferation and induced cell death, while p-cymene induced cell necrosis. These findings suggest that the essential oil from Nigella sativa has potent immunomodulatory properties, primarily attributed to thymoquinone.
BIOMEDICINE & PHARMACOTHERAPY
(2022)
Article
Endocrinology & Metabolism
Laurie G. Landry, Amanda M. Anderson, Holger A. Russ, Liping Yu, Sally C. Kent, Mark A. Atkinson, Clayton E. Mathews, Aaron W. Michels, Maki Nakayama
Summary: This study evaluated the reactivity of CD4 T cells from T1D donors to preproinsulin peptides and identified 14 TCR clonotypes that responded to these peptides. These clonotypes targeted hot spot regions in proinsulin, overlapping with previously detected CD4 T cell responses in peripheral blood of T1D patients.
FRONTIERS IN ENDOCRINOLOGY
(2021)
Article
Immunology
Christina P. Martins, Lee A. New, Erin C. O'Connor, Dana M. Previte, Kasey R. Cargill, Isabelle L. Tse, Sunder Sims-Lucas, Jon D. Piganelli
Summary: In T1D, CD4(+) T cells can be targeted and their metabolic reprogramming altered by using the small molecule PFK15 as a competitive inhibitor. This approach delayed diabetes onset in animal models, with a significant percentage of animals maintaining normal blood glucose levels. The results demonstrate a novel therapeutic strategy to control aberrant T cell responses by exploiting metabolic reprogramming in T1D.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Medicine, Research & Experimental
Elisa Balmas, Janice Chen, Alex K. Hu, Hannah A. DeBerg, Mario G. Rosasco, Vivian H. Gersuk, Elisavet Serti, Cate Speake, Carla J. Greenbaum, Gerald T. Nepom, Peter S. Linsley, Karen Cerosaletti
Summary: This study analyzed the preservation of IAR CD4+ T cells in patients with new-onset type 1 diabetes in clinical trials and found that the frequency of a unique memory phenotype cell was inversely correlated with C-peptide preservation. This may serve as a biomarker to predict treatment response.
Article
Immunology
Wei Li, Ronghui Li, Yang Wang, Yan Zhang, Munendra S. Tomar, Shaodong Dai
Summary: Calcitonin gene-related peptide (CGRP) plays a critical role in peripheral sensitization and pain development. CGRP-specific CD4 T cells were found in non-obese diabetic (NOD) mice and showed correlation with diabetic progression. Furthermore, human CGRP peptide elicited strong CGRP-specific T-cell responses. These findings suggest that CGRP could be a potential autoantigen for type 1 diabetes and CGRP-specific CD4 T cells may serve as a unique marker for the disease.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Multidisciplinary Sciences
Vikash Chandra, Hazem Ibrahim, Clementine Halliez, Rashmi B. Prasad, Federica Vecchio, Om Prakash Dwivedi, Jouni Kvist, Diego Balboa, Jonna Saarimaki-Vire, Hossam Montaser, Tom Barsby, Vaino Lithovius, Isabella Artner, Swetha Gopalakrishnan, Leif Groop, Roberto Mallone, Decio L. Eizirik, Timo Otonkoski
Summary: The TYK2 gene is crucial in the development of type 1 diabetes. In this study, the researchers demonstrate that TYK2 regulates the development of beta-cells and inhibiting TYK2 in the islets enhances their survival against CD8(+) T-cell cytotoxicity. This finding highlights TYK2 as a potential therapeutic target to halt the progression of type 1 diabetes.
NATURE COMMUNICATIONS
(2022)
Article
Engineering, Biomedical
Sofie Dragoun Kolibova, Eva Maria Woelfel, Haniyeh Hemmatian, Petar Milovanovic, Herbert Mushumba, Birgit Wulff, Maximilian Neidhardt, Klaus Pueschel, Antonio Virgilio Failla, Annegreet Vlug, Alexander Schlaefer, Benjamin Ondruschka, Michael Amling, Lorenz C. Hofbauer, Martina Rauner, Bjoern Busse, Katharina Jaehn-Rickert
Summary: Type 1 diabetes mellitus (T1DM) is associated with increased bone fragility. Our study found accelerated osteocyte apoptosis and local mineralization in T1DM patients, suggesting that T1DM speeds up bone aging and impairs its biomechanical competence. Dysfunction of the osteocyte network hampers bone remodeling and repair, contributing to the increased fracture risk in T1DM individuals.
ACTA BIOMATERIALIA
(2023)
Article
Endocrinology & Metabolism
Perrin Guyer, David Arribas-Layton, Anthony Manganaro, Cate Speake, Sandra Lord, Decio L. Eizirik, Sally C. Kent, Roberto Mallone, Eddie A. James
Summary: A recent study discovered novel splice variant and secretory granule antigens within the HLA class I peptidome of human islets, and found that CD8(+) T cells from peripheral blood and human islets recognize these antigens. Through a systematic discovery process, the study identified novel CD4(+) T cell epitopes derived from these antigens. The study further demonstrated the contribution of unconventional antigens to the loss of tolerance in autoimmune diabetes.
Article
Endocrinology & Metabolism
Perrin Guyer, David Arribas-Layton, Anthony Manganaro, Cate Speake, Sandra Lord, Decio L. Eizirik, Sally C. Kent, Roberto Mallone, Eddie A. James
Summary: A recent discovery identified novel splice variant and secretory granule antigens in human islets, which were recognized by CD8(+) T cells. This study aimed to identify CD4(+) T cell epitopes derived from these antigens and found 145 potential epitopes. The significant findings included T cells recognizing distinct epitopes derived from cyclin I splice variant, neuroendocrine convertase 2, and urocortin-3 at frequencies similar to an immunodominant proinsulin epitope, suggesting the contribution of unconventional antigens to autoimmune diabetes.
Article
Biochemistry & Molecular Biology
Jesselina Francisco dos Santos Haber, Sandra Maria Barbalho, Jose Augusto Sgarbi, Rafael Santos de Argollo Haber, Roger William de Labio, Lucas Fornari Laurindo, Eduardo Federighi Baisi Chagas, Spencer Luiz Marques Payao
Summary: This study aimed to investigate the expression of interleukin-10 (IL-10) and tumor necrosis factor-alpha (TNF-α) in type 1 diabetes mellitus (T1DM). The study found that cytokine gene expression was higher in T1DM patients, with IL-10 gene expression significantly increased in patients with ketoacidosis and positively correlated with HbA1c levels. IL-10 expression was negatively correlated with the age of diabetes patients and the time of diagnosis. TNF-α expression showed a positive correlation with age. The expression of IL-10 and TNF-α genes significantly increased in T1DM patients.
Review
Biochemistry & Molecular Biology
Ismael Valladolid-Acebes, Per-Olof Berggren, Lisa Juntti-Berggren
Summary: This review highlights the importance of exploring the role of apoCIII in inflammation and autoimmunity in relation to Type-1 diabetes, emphasizing the need for further research in this field.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Review
Immunology
James Alexander Pearson, F. Susan Wong, Li Wen
Summary: Microbiota play a crucial role in modulating susceptibility to Type 1 diabetes, with the association of microbiota composition with genetic risk and immune responses. The role of inflammasomes in Type 1 diabetes and the development of inhibitors for therapeutically targeting inflammasomes are areas that require further study.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Genetics & Heredity
Bing Yao, Tao Gui, Xiangwei Zeng, Yexuan Deng, Zhi Wang, Ying Wang, Dongjun Yang, Qixiang Li, Peipei Xu, Ruifeng Hu, Xinyu Li, Bing Chen, Jin Wang, Ke Zen, Haitao Li, Melissa J. Davis, Marco J. Herold, Hua-Feng Pan, Zhi-Wei Jiang, David C. S. Huang, Ming Liu, Junyi Ju, Quan Zhao
Summary: PRMT1-mediated H4R3me2a recruits SMARCA4, which promotes colorectal cancer progression by enhancing EGFR signaling.
Article
Hematology
Piers Blombery, Thomas E. Lew, Michael A. Dengler, Ella R. Thompson, Victor S. Lin, Xiangting Chen, Tamia Nguyen, Ashish Panigrahi, Sasanka M. Handunnetti, Dennis A. Carney, David A. Westerman, Constantine S. Tam, Jerry M. Adams, Andrew H. Wei, David C. S. Huang, John F. Seymour, Andrew W. Roberts, Mary Ann Anderson
Summary: The BCL2 inhibitor venetoclax has therapeutic roles in CLL and AML and can lead to clinical and molecular abnormalities in the myeloid compartment. Mutations in the apoptosis effector BAX may result in resistance to venetoclax. Co-occurrence of BAX mutations with DNMT3A or ASXL1 mutations was observed in clonal hematopoiesis.
Article
Biochemistry & Molecular Biology
Lahiru Gangoda, Robyn L. Schenk, Sarah A. Best, Christina Nedeva, Cynthia Louis, Damian B. D'Silva, Kirsten Fairfax, Andrew G. Jarnicki, Hamsa Puthalakath, Kate D. Sutherland, Andreas Strasser, Marco J. Herold
Summary: Inflammation is a natural defense mechanism of the body against pathogens, but its sustained presence can lead to various pathologies. The excessive activity of immune cells plays a critical role in chronic inflammation, but research suggests that A1 may not have a major impact on the survival of immune cells during inflammation.
CELL DEATH AND DIFFERENTIATION
(2022)
Article
Immunology
Nicholas A. Scott, Melissa A. E. Lawson, Ryan James Hodgetts, Gwenaelle Le Gall, Lindsay J. Hall, Elizabeth R. Mann
Summary: Intestinal macrophage metabolism is influenced by microbial metabolites. Disruption of the intestinal microbiota by antibiotics significantly alters the metabolic environment and functions of intestinal macrophages. The microbiota has compartment-specific effects on gut macrophage metabolism, which have important implications for monocyte recruitment and macrophage differentiation.
Editorial Material
Medicine, General & Internal
Robert G. Stolz, Mark R. Dowling, Belinda B. Lin, Kylie Mason, Stephen Muhi
MEDICAL JOURNAL OF AUSTRALIA
(2022)
Article
Cell Biology
Annette Jacobsen, Catia L. Pierotti, Kym N. Lowes, Amanda E. Au, Ying Zhang, Nima Etemadi, Cheree Fitzgibbon, Wilhelmus J. A. Kersten, Andre L. Samson, Mark F. van Delft, David C. S. Huang, Helene Jousset Sabroux, Guillaume Lessene, John Silke, James M. Murphy
Summary: The Lck inhibitor AMG-47a has been identified as an inhibitor of necroptosis, particularly effective in human cells. Additionally, RIPK1 is found to play a complete dependence in cell death caused by activated MLKL, with some involvement from RIPK3.
CELL DEATH & DISEASE
(2022)
Article
Hematology
Rachel Thijssen, Luyi Tian, Mary Ann Anderson, Christoffer Flensburg, Andrew Jarratt, Alexandra L. Garnham, Jafar S. Jabbari, Hongke Peng, Thomas E. Lew, Charis E. Teh, Quentin Gouil, Angela Georgiou, Tania Tan, Tirta M. Djajawi, Constantine S. Tam, John F. Seymour, Piers Blombery, Daniel H. D. Gray, Ian J. Majewski, Matthew E. Ritchie, Andrew W. Roberts, David C. S. Huang
Summary: Researchers used single-cell RNA sequencing to uncover the genetic and epigenetic changes associated with acquired resistance to Venetoclax in chronic lymphocytic leukemia (CLL). They found that these changes involve alterations in the BCL2 family of apoptosis regulators, particularly upregulation of the MCL1 gene and activation of NF-kappa B. MCL1 was identified as a direct transcriptional target of NF-kappa B. These findings highlight the plasticity of CLL cells in evading Venetoclax-induced apoptosis and provide insights for overcoming Venetoclax resistance.
Article
Audiology & Speech-Language Pathology
Gabrielle J. Miller, Barbara A. Lewis
Summary: The primary aim of this study was to compare the decoding and literacy-related skills of children with sCAS and children with RD-no SSD, and to explore the association between LI and these skills in the sCAS group. The results showed that the sCAS group performed worse than the RD-no SSD group in phonological processing, multisyllable word repetition, diadochokinetic rate, and speech-in-noise perception. Participants with sCAS + LI demonstrated deficits in literacy and literacy-related skills. Therefore, tailored interventions are needed to address reading difficulties for children with sCAS, especially those with comorbid LI.
LANGUAGE SPEECH AND HEARING SERVICES IN SCHOOLS
(2022)
Article
Biochemistry & Molecular Biology
Allan Shuai Huang, Hui San Chin, Boris Reljic, Tirta M. Djajawi, Iris K. L. Tan, Jia-Nan Gong, David A. Stroud, David C. S. Huang, Mark F. van Delft, Grant Dewson
Summary: Through a genome-wide screen, the mitochondrial E3 ubiquitin ligase MARCHF5 was identified as an important regulator of intrinsic apoptosis. Its deletion resulted in resistance to BH3-mimetic drugs and activated conformation of BAK protein, forming inhibitory complexes with pro-survival proteins.
CELL DEATH AND DIFFERENTIATION
(2023)
Article
Cell Biology
Christine Engelmann, Patrick Schuhmachers, Hana Zdimerova, Sanamjeet Virdi, Mathias Hauri-Hohl, Jana Pachlopnik Schmid, Adam Grundhoff, Rebecca A. Marsh, Wendy Wei-Lynn Wong, Christian Muenz
Summary: XLP is caused by loss of SAP or XIAP. Inhibition of XIAP leads to loss of B cells and decrease in viral titers and lymphomagenesis in humanized mice. Memory B cell loss is also observed in patients with XIAP deficiency.
CELL DEATH & DISEASE
(2022)
Article
Hematology
Amanda E. Au, Jason Corbin, Marion Lebois, Pradnya Gangatirkar, Fatme Yassinson, Stephanie R. Hyslop, Ping Cannon, Kylie D. Mason, Connie S. N. Li-Wai-Suen, Alexandra L. Garnham, Diane Moujalled, Luisa Cimmino, Warren S. Alexander, Emma C. Josefsson
Article
Oncology
Georgia S. Mills, Pietro R. Di Ciaccio, Catherine Tang, Verity Chadwick, Kylie D. Mason, Belinda A. Campbell, Michael J. Shipton, Mohamed Shanavas, Kirk L. Morris, Matthew Greenwood, Jenna Langfield, Giselle Kidson-Gerber, Renee Eslick, Xavier Badoux, Costas K. Yannakou, Shane A. Gangatharan, Ian Bilmon, Nada Hamad
Summary: Lymphoma in pregnancy is a rare and challenging diagnosis that poses unique therapeutic, social, and ethical challenges. This study provides insights into the experiences and needs of women with lymphoma during pregnancy, highlighting the importance of clear and empathic communication, tailored educational materials, psychosocial supports, and timely management of oncofertility.
LEUKEMIA & LYMPHOMA
(2022)
Article
Respiratory System
Nicholas A. Scott, Laurence Pearmain, Sean B. Knight, Oliver Brand, David J. Morgan, Christopher Jagger, Sarah Harbach, Saba Khan, Halima A. Shuwa, Miriam Franklin, Verena Kaestele, Thomas Williams, Ian Prise, Flora A. McClure, Pamela Hackney, Lara Smith, Madhvi Menon, Joanne E. Konkel, Criag Lawless, James Wilson, Alexander G. Mathioudakis, Stefan C. Stanel, Andrew Ustianowski, Gabriella Lindergard, Seema Brij, Nawar Diar Bakerly, Paul Dark, Christopher Brighting, Pilar Rivera-Ortega, Graham M. Lord, Alex Horsley, L. CIRCO, Karen Piper Hanley, Timothy Felton, Angela Simpson, John R. Grainger, Tracy Hussell, Elizabeth R. Mann
Summary: COVID-19 is associated with immune dysfunction, which may contribute to the chronic symptoms in long COVID patients. Phenotypical and functional changes in monocytes were assessed in COVID-19 patients during hospitalization and convalescence. Specific monocyte alterations were found in long COVID patients with unresolved lung injury and ongoing fatigue. These findings offer potential therapeutic opportunities for COVID-19 patients with persistent morbidity.
EUROPEAN RESPIRATORY JOURNAL
(2023)
Article
Hematology
Donia M. Moujalled, Fiona C. Brown, Chong Chyn Chua, Michael A. Dengler, Giovanna Pomilio, Natasha S. Anstee, Veronique Litalien, Ella Thompson, Thomas Morley, Sarah MacRaild, Ing S. Tiong, Rhiannon Morris, Karen Dun, Adrian Zordan, Jaynish Shah, Sebastien Banquet, Ensar Halilovic, Erick Morris, Marco J. Herold, Guillaum Lessene, Jerry M. Adams, David C. S. Huang, Andrew W. Roberts, Piers Blombery, Andrew H. Wei
Summary: Randomized trials have shown that the combination of the BCL-2 inhibitor venetoclax with azacitidine improves survival in older AML patients, and ongoing clinical trials are testing venetoclax in combination with intensive chemotherapy in fitter patients. However, a significant number of patients still relapse, highlighting the need for a better understanding of relapse mechanisms.
Review
Oncology
Sarah T. Diepstraten, Mary Ann Anderson, Peter E. Czabotar, Guillaume Lessene, Andreas Strasser, Gemma L. Kelly
Summary: Apoptosis is a programmed cell death regulated by BCL-2 family proteins. BH3-mimetic drugs have been developed to target prosurvival proteins in cancer cells. These drugs are designed to induce apoptosis and have shown efficacy in certain cancers but faces challenges like resistance and toxic effects.
NATURE REVIEWS CANCER
(2022)