Article
Biochemistry & Molecular Biology
Angela M. Mitchell, Aaron W. Michels
Summary: Despite progress in understanding the mechanisms behind autoimmune diseases, there is limited knowledge about protective mechanisms against these diseases. In the case of type 1 diabetes, pathogenic T cells that destroy pancreatic islets are well understood, but the immune-mediated mechanisms that contribute to protection against this disease are not fully elucidated. One potential protective mechanism involves regulatory CD4 T cells that suppress immune responses by recognizing self-peptides from islets. This review summarizes current knowledge about the antigenic self-peptides recognized by Tregs in the context of type 1 diabetes.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Review
Endocrinology & Metabolism
Matthew A. Budd, Mahdis Monajemi, Sarah J. Colpitts, Sarah Q. Crome, C. Bruce Verchere, Megan K. Levings
Summary: Type 1 diabetes is caused by defects in immune self-tolerance, and certain immune cell populations may have the capacity to promote tolerance and support the regeneration of beta cells. Recent research has shown that macrophages, regulatory T cells, and innate lymphoid cells may play dual roles in immune regulation and tissue regeneration in the context of type 1 diabetes.
Article
Multidisciplinary Sciences
Scott A. Ochsner, Rudolf T. Pillich, Deepali Rawool, Jeffrey S. Grethe, Neil J. McKenna
Summary: This article describes how investigator-generated transcriptomic datasets can be repurposed to generate hypotheses about the signaling pathways of circulating immune cells in type 1 diabetes. By computing and validating sets of differentially expressed genes, as well as inferring and validating signaling node networks, the study demonstrated the value of these datasets in understanding the pathogenesis of T1D and generating actionable hypotheses. Additionally, a federated, cloud-based web resource was developed to provide unrestricted access and re-use of the data matrix by the research community.
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
Melanie R. Shapiro, Xiaoru Dong, Daniel J. Perry, James M. McNichols, Puchong Thirawatananond, Amanda L. Posgai, Leeana D. Peters, Keshav Motwani, Richard S. Musca, Andrew Muir, Patrick Concannon, Laura M. Jacobsen, Clayton E. Mathews, Clive H. Wasserfall, Michael J. Haller, Desmond A. Schatz, Mark A. Atkinson, Maigan A. Brusko, Rhonda L. Bacher, Todd M. Brusko
Summary: This study investigates the immune cell subsets in peripheral blood and their changes in individuals with type 1 diabetes (T1D). The researchers found accelerated immune aging in T1D and identified phenotypes associated with the disease. These findings provide insights for biomarker monitoring and therapeutic interventions.
Article
Endocrinology & Metabolism
Andrea Vecchione, Tatiana Jofra, Jolanda Gerosa, Kimberly Shankwitz, Roberta Di Fonte, Giuseppe Galvani, Elio Ippolito, Maria Pia Cicalese, Andrew R. Schultz, Howie R. Seay, Mariagrazia Favellato, Giulia Milardi, Angela Stabilini, Francesca Ragogna, Pauline Grogan, Eleonora Bianconi, Andrea Laurenzi, Amelia Caretto, Rita Nano, Raffaela Melzi, Nichole Danzl, Emanuele Bosi, Lorenzo Piemonti, Alessandro Aiuti, Todd Brusko, Constantinos Petrovas, Manuela Battaglia, Georgia Fousteri
Summary: The study found significantly reduced frequency of Tfr cells in the spleen and pancreatic lymph nodes of T1D patients, while no significant differences were observed in the frequency and phenotype of blood Tfr cells. Adoptive transfer of Tfr cells in a mouse model of T1D delayed disease development, indicating an important role for Tfr cells in maintaining peripheral tolerance and regulating autoreactive Tfh cells.
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.
Review
Biochemistry & Molecular Biology
Iwona Ben-Skowronek, Joanna Sieniawska, Emilia Pach, Wiktoria Wrobel, Anna Skowronek, Zaklina Tomczyk, Iga Rosolowska
Summary: This study evaluated innovative immune interventions as treatments for T1DM and found that Treg cells play an important role in limiting the development of T1DM. The activation or application of Tregs may be more effective in the early stages of T1DM development. However, the therapeutic use of Treg cells in T1DM requires long-term observation in a large group of patients.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Review
Immunology
Joanne Boldison, F. Susan Wong
Summary: Regulatory B cells (Bregs) play an anti-inflammatory role through both cytokine secretion and cell-contact mediated mechanisms. While IL-10 secretion is a hallmark feature of Bregs, IL-35 and TGF beta-producing B cells have also been identified. Reports identifying impaired frequency or function of Bregs in individuals with type 1 diabetes are limited, leading to a restricted understanding of the role played by these Breg subsets in the pathogenesis of the condition.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Immunology
Nicolas Krause, Joerg Mengwasser, Elpida Phithak, Francisca Beato, Marc Appis, Edgar Louis Milford, Johan Pratschke, Igor Sauer, Anja Kuehl, Arndt Vogel, Michael Goodyear, Linda Hammerich, Frank Tacke, Johanna Faith Haas, Tobias Mueller, Nalan Utku
Summary: IR1 cells are a subset of T regulatory cells that have immune suppressive functions and can inhibit proliferation in mixed lymphocyte reactions. They deliver regulatory signals by binding to their ligand, HLA-DR alpha 2, and have the potential to modulate immune dysregulation.
FRONTIERS IN IMMUNOLOGY
(2022)
Review
Health Care Sciences & Services
Claire Deligne, Sylvaine You, Roberto Mallone
Summary: Our understanding of the immunopathological features of type 1 diabetes has improved, and personalized treatment based on disease stage and patient characteristics could enhance therapeutic efficacy.
JOURNAL OF PERSONALIZED MEDICINE
(2022)
Article
Biology
Jeremy R. B. Newman, S. Alice Long, Cate Speake, Carla J. Greenbaum, Karen Cerosaletti, Stephen S. Rich, Suna Onengut-Gumuscu, Lauren M. McIntyre, Jane H. Buckner, Patrick Concannon
Summary: Transcriptomic analysis suggests that changes in splicing machinery in memory CD4+ CD25- or CD4+ CD25+ T lymphocytes could contribute to the pathophysiology of type 1 diabetes (T1D).
COMMUNICATIONS BIOLOGY
(2023)
Article
Chemistry, Multidisciplinary
Sungwook Jung, Moufida Ben Nasr, Baharak Bahmani, Vera Usuelli, Jing Zhao, Gianmarco Sabiu, Andy Joe Seelam, Said Movahedi Naini, Hari Baskar Balasubramanian, Youngrong Park, Xiaofei Li, Salma Ayman Khalefa, Vivek Kasinath, MacKenzie D. Williams, Ousama Rachid, Yousef Haik, George C. Tsokos, Clive H. Wasserfall, Mark A. Atkinson, Jonathan S. Bromberg, Wei Tao, Paolo Fiorina, Reza Abdi
Summary: A novel and specific nanodelivery platform targeting high endothelial venules (HEVs) in pancreatic lymph nodes (PLNs) and pancreas is developed to address the limited efficacy, equipoise, or safety issues of immune therapeutics in treating type 1 diabetes (T1D). By encapsulating anti-CD3 mAb in poly(lactic-co-glycolic acid)-poly(ethylene glycol) nanoparticles (NPs) conjugated with MECA79 mAb, the targeted delivery of these NPs improves the accumulation of anti-CD3 mAb in both PLNs and pancreas of nonobese diabetic (NOD) mice. Treatment with MECA79-anti-CD3-NPs significantly reverses T1D in hyperglycemic NOD mice by reducing T effector cell populations and pro-inflammatory cytokine production in PLNs.
ADVANCED MATERIALS
(2023)
Review
Immunology
Patricia Sole, Pere Santamaria
Summary: Systemic delivery of pMHC class II-based nanomedicines can re-program CD4+ T cells into TR1-like cells, which suppress organ-specific autoimmunity effectively. The true identity and direct precursors of TR1-like cells remain unclear, and further transcriptional and epigenetic characterization of homogeneous pools of these cells is needed to unravel this mystery.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Immunology
Li Zhou, Xuemin He, Peihong Cai, Ting Li, Rongdong Peng, Junlong Dang, Yue Li, Haicheng Li, Feng Huang, Guojun Shi, Chichu Xie, Yan Lu, Yanming Chen
Summary: The study found that TGF-beta-induced Tregs could ameliorate the development of T1D and preserve beta cell function in a mouse model. The preventive effect was associated with the inhibition of Tc1 cell function and rebalancing the Treg/Tc1 cell ratio. The underlying mechanisms involved the combinatorial actions of mTOR and TCF1 mediated by TGF-beta.
CELLULAR & MOLECULAR IMMUNOLOGY
(2021)