Article
Immunology
Mahima T. Rasquinha, Ninaad Lasrado, Meghna Sur, Kiruthiga Mone, Haowen Qiu, Jean-Jack Riethoven, Raymond A. Sobel, Jay Reddy
Summary: In this study, a live-attenuated CVB3 vaccine virus called Mt10 was developed, which protected genetically predisposed NOD mice from CVB4-triggered type 1 diabetes but did not alter the subsequent development of spontaneous diabetes. The vaccine induced significant levels of neutralizing antibodies, mainly of the IgG2c isotype, and the virus was not detected in vaccinated animals. Monitoring blood glucose levels and insulin antibodies helped predict vaccine responses.
Article
Food Science & Technology
Keiko Kataoka, Hideyuki Nemoto, Akiko Sakurai, Koji Yasutomo, Masataka Shikanai
Summary: The consumption of brown rice and rice bran fermented with Aspergillus oryzae (FBRA) can suppress spontaneously occurring diabetes in female NOD mouse, probably by maintaining the number of intact islets.
JOURNAL OF FUNCTIONAL FOODS
(2021)
Article
Immunology
Ashley E. Ciecko, David M. Schauder, Bardees Foda, Galina Petrova, Moujtaba Y. Kasmani, Robert Burns, Chien-Wei Lin, William R. Drobyski, Weiguo Cui, Yi-Guang Chen
Summary: In prediabetic NOD mice islets, two functionally distinct subsets of activated CD8 T cells were identified, with one subset expressing higher levels of inhibitory and cytotoxic molecules and being more prone to apoptosis. CD44(high)TCF1(+)CXCR6(-) CD8 T cells were found to promote insulitis and T1D development more effectively through continuous generation of a more cytotoxic CD44(high)TCF1(-)CXCR6(+) subset. Signaling through IL-27 was shown to promote the differentiation of CD44(high)TCF1(+)CXCR6(-) CD8 T cells into the terminal effector population CD44(high)TCF1(-)CXCR6(+).
JOURNAL OF IMMUNOLOGY
(2021)
Article
Endocrinology & Metabolism
Xiangqian Li, Lina Wang, Gang Meng, Xiaoling Chen, Shushu Yang, Mengjun Zhang, Zhengni Zheng, Jie Zhou, Zhu Lan, Yuzhang Wu, Li Wang
Summary: This study provides evidence for the negative impact of high glucose intake as a dietary factor on the pathogenesis of type 1 diabetes. Therefore, avoiding high sugar intake may be an effective disease prevention strategy for children or adults susceptible to type 1 diabetes.
FRONTIERS IN ENDOCRINOLOGY
(2022)
Article
Endocrinology & Metabolism
Tatiane M. Preisser, Vanessa P. da Cunha, Mariana P. Santana, Vanessa B. Pereira, Denise C. Cara, Bianca M. Souza, Anderson Miyoshi
Summary: By administering Lactococcus lactis MG1363 strains carrying plasmids encoding IL-4 and IL-10 in STZ-induced and NOD mouse models, the study demonstrates a promising treatment approach for T1D. The combination of IL-4 and IL-10-expressing bacterial strains showed better prevention of diabetes, preservation of pancreatic islets, and reduced inflammation in treated mice.
JOURNAL OF DIABETES RESEARCH
(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
Biochemistry & Molecular Biology
Jide Tian, Blake Middleton, Victoria Seunghee Lee, Hye Won Park, Zhixuan Zhang, Bokyoung Kim, Catherine Lowe, Nancy Nguyen, Haoyuan Liu, Ryan S. Beyer, Hannah W. Chao, Ryan Chen, Davis Mai, Karen Anne O'Laco, Min Song, Daniel L. Kaufman
Summary: The expression of gamma-aminobutyric acid receptors in immune cells may have therapeutic potential in diseases like T1D, multiple sclerosis, rheumatoid arthritis, and COVID-19. Specific modulation of GABA(B)-Rs with agonists like lesogaberan shows promise in restoring normoglycemia and improving T1D remission rates in mouse models. The analysis of gene expression databases suggests a common feature of GABA receptors and production/secretion-related genes in immune cells.
Article
Medicine, Research & Experimental
Sarah K. Popp, Federica Vecchio, Debra J. Brown, Riho Fukuda, Yuri Suzuki, Yuma Takeda, Rikako Wakamatsu, Mahalakshmi A. Sarma, Jessica Garrett, Anna Giovenzana, Emanuele Bosi, Antony R. A. Lafferty, Karen J. Brown, Elizabeth E. Gardiner, Lucy A. Coupland, Helen E. Thomas, Beng H. Chong, Christopher R. Parish, Manuela Battaglia, Alessandra Petrelli, Charmaine J. Simeonovic
Summary: Platelet-neutrophil aggregates (PNAs) play a role in facilitating neutrophil activation and migration during the pathogenesis of type 1 diabetes (T1D). Elevated PNAs were observed in T1D patients and mice, as well as in isolated islets/insulitis, accompanied by increased islet-associated neutrophil extracellular trap (NET) products. Histones and NETs induced islet cell damage, which was prevented by the drug mCBS. PNAs could therefore serve as a biomarker for T1D autoimmunity and potentially be used for early diagnosis.
Article
Endocrinology & Metabolism
Joanne Boldison, Terri C. Thayer, Joanne Davies, F. Susan Wong
Summary: Naturally protected NOD mice exhibit unique characteristics in their pancreatic islet morphology and immune infiltrate, with features such as increased frequency of insulin-containing, smaller-sized islets and regulatory T and B cell phenotypes. Despite being diabetes free, they still have significant immune infiltrate, indicating a distinct islet signature and providing new insights into regulatory mechanisms in pancreatic islets.
Article
Cardiac & Cardiovascular Systems
Ygor Schleier, Oscar Moreno-Loaiza, Maria Micaela Lopez Alarcon, Eduarda Gabrielle Lopes Martins, Bruno Cabral Braga, Isalira Peroba Ramos, Antonio Galina, Emiliano Horacio Medei
Summary: This study found that NOD mice recapitulate cardiac disturbances observed in type 1 diabetes patients, including reduced heart weight, prolonged ECG intervals, and arrhythmias.
JOURNAL OF CARDIOVASCULAR TRANSLATIONAL RESEARCH
(2021)
Review
Immunology
Ida Pastore, Emma Assi, Moufida Ben Nasr, Andrea Mario Bolla, Anna Maestroni, Vera Usuelli, Cristian Loretelli, Andy Joe Seelam, Ahmed Abdelsalam, Gian Vincenzo Zuccotti, Francesca D'Addio, Paolo Fiorina
Summary: Although progress has been made in understanding the pathophysiological mechanisms of T1D, the quest for effective therapeutic options is ongoing. Promising results have been seen with HSC-based approaches and teplizumab, but more research is needed to establish their long-term efficacy and safety. Genetically engineered HSCs hold potential as a novel biologic therapy for T1D and other autoimmune/immune-related disorders, with studies in murine models and humanized mouse models showing accelerated translational potentials.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Immunology
Qin Zeng, Jianfeng Song, Dandan Wang, Xiaoxiao Sun, Yalun Xiao, Haowei Zhang, Yang Xiao, Zhiguang Zhou, Tuo Deng
Summary: In this study, we identified sorafenib as a potential inhibitor of Th1 cell differentiation through screening an FDA-approved tyrosine kinase inhibitor drug library. Treatment with sorafenib inhibited Th1 cell population and impeded the development of type 1 diabetes in NOD mice. Mechanistically, sorafenib indirectly inhibited JAK2 activity.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Kailash Singh, Orian Bricard, Jeason Haughton, Mikaela Bjorkqvist, Moa Thorstensson, Zhengkang Luo, Loriana Mascali, Emanuela Pasciuto, Chantal Mathieu, James Dooley, Adrian Liston
Summary: This article discusses the causes and mechanisms of insulin-producing beta-cell death in type 1 diabetes. Cellular stress is found to contribute to the loss of beta-cells. By enhancing the expression of the anti-apoptotic protein Manf, the robustness of beta-cells can be improved, leading to a lower incidence of type 1 diabetes.
Article
Immunology
Gaurang Jhala, Claudia Selck, Jonathan Chee, Chun-Ting J. Kwong, Evan G. Pappas, Helen E. Thomas, Thomas W. H. Kay, Balasubramanian Krishnamurthy
Summary: T-cell responses to insulin and proinsulin play a central role in islet autoimmunity in humans and NOD mice. Knockout of proinsulin-1 can protect NOD mice from autoimmune diabetes, while transgenic NOD mice with regulated proinsulin-1 expression display reduced incidence of spontaneous diabetes. Boosting immune tolerance to proinsulin-1 partially prevents islet autoimmunity in NOD mice, with minimal impact on responses to other antigens.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Multidisciplinary Sciences
F. Szymczak, M. L. Colli, M. J. Mamula, C. Evans-Molina, D. L. Eizirik
Summary: Research has shown that autoimmune diseases exhibit similar molecular signatures in target tissues, with many related to interferon signaling, which could be targeted for therapy. This suggests that future studies should focus on both the immune system and target tissues, and their interactions.
Article
Biochemistry & Molecular Biology
Euphrasie Kawila Mafanda, Rajani Kandhi, Diwakar Bobbala, Md Gulam Musawwir Khan, Madhuparna Nandi, Alfredo Menendez, Sheela Ramanathan, Subburaj Ilangumaran
Article
Oncology
Md Gulam Musawwir Khan, Amit Ghosh, Bhavesh Variya, Madanraj Appiya Santharam, Awais Ullah Ihsan, Sheela Ramanathan, Subburaj Ilangumaran
Article
Biochemistry & Molecular Biology
Madanraj Appiya Santharam, Akhil Shukla, Awais Ullah Ihsan, Maryse Cloutier, Dominique Levesque, Sheela Ramanathan, Francois-Michel Boisvert, Subburaj Ilangumaran
Summary: SOCS1 functions as a tumor suppressor in hepatocellular carcinoma and many other cancers by inhibiting tyrosine kinases, promoting ubiquitination and proteasomal degradation, and modulating transcription factors. This study found that SOCS1 modulates the hepatocyte proteome and regulates signaling pathways, particularly involving the HGF receptor MET RTK.
Review
Biochemistry & Molecular Biology
Maryse Cloutier, Madhuparna Nandi, Awais Ullah Ihsan, Hugues Allard Chamard, Subburaj Ilangumaran, Sheela Ramanathan
Review
Biochemistry & Molecular Biology
Hugues Allard-Chamard, Hemant K. Mishra, Madhuparna Nandi, Marian Mayhue, Alfredo Menendez, Subburaj Ilangumaran, Sheela Ramanathan
Review
Biochemistry & Molecular Biology
Akhil Shukla, Maryse Cloutier, Madanraj Appiya Santharam, Sheela Ramanathan, Subburaj Ilangumaran
Summary: The immune system constantly monitors and eliminates cancerous cells, with CD8(+) cytotoxic T lymphocytes playing a key role in tumor cell killing. Cancer cells evade immune surveillance by downregulating MHC-I and key proteins of the antigen processing and presentation machinery. NLRC5 has been identified as the key transcriptional activator of MHC-I and APM genes, and genetic lesions and epigenetic modifications of NLRC5 are common causes of MHC-I defects in cancers.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Review
Immunology
Marc-Andre Limoges, Maryse Cloutier, Madhuparna Nandi, Subburaj Ilangumaran, Sheela Ramanathan
Summary: Long-term survival of T lymphocytes is crucial for maintaining cell numbers, and the GIMAP family of proteins plays a significant role in this process. Recent studies suggest that GIMAP proteins may interact with each other and be involved in the cellular cargo movement.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Immunology
Madhuparna Nandi, Mitterrand Muamba Moyo, Sakina Orkhis, Jeanne Masunga Faida Mobulakani, Marc-Andre Limoges, Fjolla Rexhepi, Marian Mayhue, Anny Armas Cayarga, Gisela Cofino Marrero, Subburaj Ilangumaran, Alfredo Menendez, Sheela Ramanathan
Summary: Interleukin-15 (IL-15) regulates immune cell activity by forming a trimeric complex with IL-15Rα, but can also signal through the IL-15Rβγ(c) dimer. IL-15 deficiency results in the inability to control bacterial infections, while mice lacking IL-15Rα are able to effectively clear pathogens.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Immunology
Akouavi Julite I. Quenum, Akhil Shukla, Fjolla Rexhepi, Maryse Cloutier, Amit Ghosh, Thomas A. Kufer, Sheela Ramanathan, Subburaj Ilangumaran
Summary: NLRC5 deficiency disrupts hepatic inflammatory response following chemical injury, but does not significantly aggravate the fibrogenic response. Increased phosphorylation of the NF-kappa B subunit p65 was observed in fibrotic livers of NLRC5-deficient mice, indicating that NLRC5 is not a critical regulator of liver fibrosis pathogenesis.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Anatomy & Morphology
Rajani Kandhi, Bhavesh Variya, Sheela Ramanathan, Subburaj Ilangumaran
Summary: This article describes an efficient method for isolating intrahepatic leukocytes from mice fed with high fat diet and proposes a strategy to alleviate autofluorescence during phenotyping by multicolor flow cytometry. The article also introduces a gating strategy for robust identification of different immune cell subsets. These procedures allow simultaneous processing of multiple samples and ensure reliable cell isolation and noise reduction for reliable characterization of intrahepatic leukocytes from fatty liver tissues.
ANATOMICAL RECORD-ADVANCES IN INTEGRATIVE ANATOMY AND EVOLUTIONARY BIOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Akouavi Julite Irmine Quenum, Madanraj Appiya Santharam, Sheela Ramanathan, Subburaj Ilangumaran
Summary: Cytokine priming enhances antigen responsiveness and functional fitness of naive CD8(+) T cells by modulating chromatin accessibility. This study reveals the molecular mechanisms underlying cytokine priming and its impact on gene expression, suggesting its significance in immune response and regulation.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Oncology
Md Gulam Musawwir Khan, Nadia Boufaied, Mehdi Yeganeh, Rajani Kandhi, Stephanie Petkiewicz, Ankur Sharma, Akihiko Yoshimura, Gerardo Ferbeyre, David P. Labbe, Sheela Ramanathan, Subburaj Ilangumaran
Summary: The SOCS1 protein protects liver cells from becoming cancerous and its deficiency increases susceptibility to liver cancer. CDKN1A is a protein that can protect against liver cancer but under certain circumstances, it can promote cancer growth. Our findings show that SOCS1 suppresses the expression of CDKN1A, preventing liver cells from withstanding the stress associated with cancer growth. This pathway could be targeted for therapeutic strategies in SOCS1-deficient liver cancers.
Article
Oncology
Madhuparna Nandi, Amit Ghosh, Sara Ali Akbari, Diwakar Bobbala, Marie-Josee Boucher, Alfredo Menendez, Trang Hoang, Subburaj Ilangumaran, Sheela Ramanathan
Summary: Leukemia is a group of hematopoietic malignancies that cause high morbidity and mortality. The deficiency of IL-15 signaling leads to poor prognosis in T-ALL patients and requires new treatment approaches. Through studying a mouse model, it was found that IL-15 deficiency resulted in the expansion of abnormal T cells and impaired DNA repair in developing cells. Additionally, increased NOTCH1 activation and survival signals provided by cytokines and growth factors were also found in pre-leukemic cells.
Article
Biochemistry & Molecular Biology
Madanraj Appiya Santharam, Akhil Shukla, Dominique Levesque, Thomas A. Kufer, Francois-Michel Boisvert, Sheela Ramanathan, Subburaj Ilangumaran
Summary: Aggressive tumors avoid immune attack by suppressing MHC-I expression. NLRC5 is a transcriptional activator of MHC-I, and defects in NLRC5 result in MHC-I defects. Restoring NLRC5 expression in poorly immunogenic B16 melanoma cells induces MHC-I and antitumor immunity, suggesting the potential use of NLRC5 for tumor immunotherapy.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Gastroenterology & Hepatology
Rajani Kandhi, Alfredo Menendez, Sheela Ramanathan, Subburaj Ilangumaran
Summary: This study reveals the crucial regulatory functions of SOCS1 in hepatic stellate cells (HSCs) during non-alcoholic fatty liver disease (NAFLD)-induced liver fibrosis. Lack of SOCS1 in HSCs leads to increased inflammation and aggravated liver fibrosis.
JOURNAL OF CLINICAL AND EXPERIMENTAL HEPATOLOGY
(2024)