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
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)
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
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
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
Immunology
Dawei Chen, Dimitri Kakabadse, Sigal Fishman, Hadas Weinstein-Marom, Joanne Davies, Joanne Boldison, Terri C. Thayer, Li Wen, Gideon Gross, F. Susan Wong
Summary: This study proposes a novel therapeutic approach using B lymphocytes to attract and regulate specific T cells, thereby preventing the development of autoimmune diabetes. By expressing chimeric MHC-peptide constructs in B cells, the engineered cells successfully inhibited cytotoxicity of antigen-specific CD8(+) T cells and induced regulatory markers in antigen-specific CD4+ T cells. Furthermore, these engineered B cells protected mice from autoimmune diabetes induced by transfer of antigen-specific T cells.
FRONTIERS IN IMMUNOLOGY
(2023)
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
Multidisciplinary Sciences
Lihua Zhu, Guangmei Song, Xiaohui Chen, Yue Zhang, Yanjie Cui, Jie Qiao, Xinran Huang, Xueqin Li, Xiaoen Liu, Xiangbo Zeng, Yangqiu Li, Liang Wang, Bo Li
Summary: This study investigated the characteristics of CD4(+)CD40(+)T cells (Th40 cells) in Chinese systemic lupus erythematosus (SLE) patients. The percentage of Th40 cells in SLE patients was significantly higher than in healthy individuals. Th40 cell percentage was associated with SLE disease activity and severity, and therapeutic efficacy. Th40 cells may be used as predictors for SLE disease activity and treatment outcomes.
SCIENTIFIC REPORTS
(2023)
Article
Endocrinology & Metabolism
Ylke Bruggeman, Pieter-Jan Martens, Gabriele Sassi, Marijke Viaene, Clive H. Wasserfall, Chantal Mathieu, Conny Gysemans
Summary: This study investigates the dynamics and phenotypes of immune cells infiltrating the pancreas and their changes in peripheral blood during the development of type 1 diabetes (T1D) in non-obese diabetic (NOD) mice. The early stages of T1D are characterized by an influx of dendritic cells and neutrophils in the pancreas. CD4+ and CD8+ T cells migrate from the pancreatic draining lymph nodes to the pancreas, coinciding with increased beta cell autoimmunity and insulitis severity. These findings provide important insights into the disease process and may contribute to the development of new therapies.
FRONTIERS IN ENDOCRINOLOGY
(2023)
Article
Immunology
Brian D. Stadinski, Sarah B. Cleveland, Michael A. Brehm, Dale L. Greiner, Priya G. Huseby, Eric S. Huseby
Summary: Type 1 diabetes is associated with the expression of specific major histocompatibility complex class II beta chain polymorphisms. The protective effect of heterozygous expression of major histocompatibility complex class II is due to non-cognate thymocyte negative selection. Heterozygous expression of the diabetes-protective allele induces negative selection of T cells, resulting in protection against autoimmunity.
Article
Endocrinology & Metabolism
Emi Kawada-Horitani, Shunbun Kita, Tomonori Okita, Yuto Nakamura, Hiroyuki Nishida, Yoichi Honma, Shiro Fukuda, Yuri Tsugawa-Shimizu, Junji Kozawa, Takaaki Sakaue, Yusuke Kawachi, Yuya Fujishima, Hitoshi Nishizawa, Miyuki Azuma, Norikazu Maeda, Iichiro Shimomura
Summary: The study found that systemic administration of MSC therapy can prevent the development of type 1 diabetes. MSCs reduced the accumulation of T cells and CXCL9-positive macrophages in the islets induced by PD-1/PD-L1 blockade, thereby decreasing the occurrence of diabetes.
Review
Immunology
Manuel Rojas, Luke S. Heuer, Weici Zhang, Yi-Guang Chen, William M. Ridgway
Summary: Autoimmunity is caused by a combination of genetic susceptibility and environmental provocation, leading to a loss of immune tolerance to self-proteins and the generation of autoreactive T and B cells. The Cd137 gene plays a crucial role in the immune response and its regulation, affecting the balance between regulatory and effector signals. Understanding the genetic control of T regulatory cell development and function is important for autoimmunity research.
FRONTIERS IN IMMUNOLOGY
(2022)
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
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
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
Immunology
Braxton L. Jamison, Tobias Neef, Andrew Goodspeed, Brenda Bradley, Rocky L. Baker, Stephen D. Miller, Kathryn Haskins
JOURNAL OF IMMUNOLOGY
(2019)
Article
Endocrinology & Metabolism
Rocky L. Baker, Marynette Rihanek, Anita C. Hohenstein, Maki Nakayama, Aaron Michels, Peter A. Gottlieb, Kathryn Haskins, Thomas Delong
Review
Endocrinology & Metabolism
Rocky L. Baker, Braxton L. Jamison, Kathryn Haskins
CURRENT OPINION IN ENDOCRINOLOGY DIABETES AND OBESITY
(2019)
Article
Endocrinology & Metabolism
David Arribas-Layton, Perrin Guyer, Thomas Delong, Mylinh Dang, I-Ting Chow, Cate Speake, Carla J. Greenbaum, William W. Kwok, Rocky L. Baker, Kathryn Haskins, Eddie A. James
Meeting Abstract
Endocrinology & Metabolism
Alyssa J. Shepherd, Martin Yussman, David H. Wagner, Gisela M. Vaitaitis
Meeting Abstract
Endocrinology & Metabolism
David H. Wagner, Gisela M. Vaitaitis
Article
Immunology
Ying Lu, Max Xu, Cayce E. Dorrier, Ray Zhang, Christian T. Mayer, David Wagner, Dorian B. McGavern, Richard J. Hodes
Summary: CD40 plays an essential role in driving autoimmune diseases in the central nervous system (CNS). It orchestrates distinct effector programs in dendritic cells (DCs) and B cells, leading to the activation of pathogenic T cells and the production of disease-causing antibodies, respectively.
JOURNAL OF IMMUNOLOGY
(2022)
Article
Immunology
Christian Curran, Gisela Vaitaitis, Dan Waid, Timothy Volmer, Enrique Alverez, David H. Wagner
Summary: Treating multiple sclerosis has been challenging, but Ocrelizumab has shown success in treating both chronic relapsing and progressive forms of the disease. In a study, it was found that TH40 cells, which are pathogenic effector T cells, increased in number during the earliest stage of multiple sclerosis (clinically isolated syndrome) and remained expanded in progressive forms of the disease. However, treatment with Ocrelizumab reduced TH40 cell numbers to healthy levels and decreased the production of inflammatory cytokines.
JOURNAL OF NEUROIMMUNOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Gisela M. Vaitaitis, David H. Wagner Jr
Summary: CD40 signaling is an important target in autoimmunity. Blocking the CD40-CD154 pathway using monoclonal antibodies during clinical trials led to severe adverse events. A peptide called KGYY15 has shown promise in preventing type 1 diabetes and reversing hyperglycemia by normalizing effector T-cell levels. The peptide also interacts with integrins CD11a/CD18 and CD11b/CD18, complicating our understanding of the inflammatory nexus and how to prevent autoinflammation.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2023)
Article
Immunology
Fernanda M. Frank, David H. Wagner Jr, Miriam Postan, Patricia B. Petray
Summary: The CD40/CD40L interaction plays a dual role in Trypanosoma cruzi infection, depending on the timing of treatment initiation. Early treatment with CD40-targeted peptide leads to uncontrolled acute infection and marked tissue damage, while late treatment improves myocardial and skeletal muscle damage.
MICROBIAL PATHOGENESIS
(2023)
Meeting Abstract
Immunology
Ying Lu, Max Xu, Ray Zhang, David H. Wagner, Richard Hodes
JOURNAL OF IMMUNOLOGY
(2021)
Meeting Abstract
Medicine, General & Internal
C. D. Curran, D. H. Wagner, T. L. Vollmer
JOURNAL OF INVESTIGATIVE MEDICINE
(2020)
Article
Endocrinology & Metabolism
Ercument Dirice, Sevim Kahraman, Dario F. De Jesus, Abdelfattah El Ouaamari, Giorgio Basile, Rocky L. Baker, Burcu Yigit, Paul D. Piehowski, Mi-Jeong Kim, Alexander J. Dwyer, Raymond W. S. Ng, Cornelia Schuster, Heidrun Vethe, Tijana Martinov, Yuki Ishikawa, Adrian Kee Keong Teo, Richard D. Smith, Jiang Hu, Kathryn Haskins, Thomas Serwold, Wei-Jun Qian, Brian T. Fife, Stephan Kissler, Rohit N. Kulkarni
Meeting Abstract
Immunology
Martin Yussman, David H. Wagner, Gisela Vaitaitis, Dan Waid
JOURNAL OF IMMUNOLOGY
(2019)
Meeting Abstract
Immunology
David H. Wagner, Gisela Vaitaitis, Dan Waid
JOURNAL OF IMMUNOLOGY
(2019)
Article
Immunology
Shane Kelly, Katherine J. L. Jackson, Timothy J. Peters, Dan Suan, Christopher C. Goodnow
Summary: This study successfully identified and characterized PR3-specific B cells from the peripheral blood of patients with PR3 autoantibodies. These cells exhibited specific immunological features, suggesting that PR3 self-reactivity may occur early in B-cell development.
JOURNAL OF AUTOIMMUNITY
(2024)
Article
Immunology
Ana Merino-Vico, Jan Piet van Hamburg, Paul Tuijnenburg, Giulia Frazzei, Aram Al-Soudi, Carlo G. Bonasia, Boy Helder, Abraham Rutgers, Wayel H. Abdulahad, Coen A. Stegeman, Jan-Stephan Sanders, Laura Bergamaschi, Paul A. Lyons, Theo Bijma, Laura van Keep, Kirsten Wesenhagen, Aldo Jongejan, Henric Olsson, Niek de Vries, Taco W. Kuijpers, Peter Heeringa, Sander W. Tas
Summary: B lineage cells play a critical role in ANCA-associated vasculitis (AAV), and the transcription factor NF-kappa B may be a potential therapeutic target for AAV and other autoimmune diseases with prominent B cell involvement.
JOURNAL OF AUTOIMMUNITY
(2024)
Article
Immunology
Christopher Nelke, Thomas Muentefering, Derya Cengiz, Lukas Theissen, Vera Dobelmann, Christina B. Schroeter, Helena Block, Corinna Preu, Alexander P. E. Michels, Stefanie Lichtenberg, Marc Pawlitzki, Steffen Pfeuffer, Niklas Huntemann, Alexander Zarbock, Thorben Briese, Christoph Kittl, Carsten Dittmayer, Thomas Budde, Ingrid E. Lundberg, Werner Stenzel, Sven G. Meuth, Tobias Ruck
Summary: K2P2.1 plays a regulatory role in the autoimmune response of idiopathic inflammatory myopathies (IIMs), by regulating inflammatory cell response, adhesion, and transmigration in both endothelial and skeletal muscle cells. Inhibiting K2P2.1 enhances the inflammatory response, while activating K2P2.1 improves the disease course.
JOURNAL OF AUTOIMMUNITY
(2024)
Article
Immunology
Xuan Zhang, Jun Xia, Ying Jiang, David S. Pisetsky, Josef S. Smolen, Rong Mu, Shengming Dai, Michael E. Weinblatt, Tore K. Kvien, Juan Li, Thomas Doerner, Yu Zhang, Liwei Lu, Chengde Yang, Pingting Yang, Yuan Zhang, Chenchen Xu, Zhan Zhao, Peter E. Lipsky
Summary: The study suggests that TwHF may be as effective as MTX in treating active RA, and combination therapy may be more effective than monotherapy.
JOURNAL OF AUTOIMMUNITY
(2024)
Article
Immunology
Maya F. Amjadi, Maxwell H. Parker, Ryan R. Adyniec, Zihao Zheng, Alex M. Robbins, S. Janna Bashar, Michael F. Denny, Sara S. Mccoy, Irene M. Ong, Miriam A. Shelef
Summary: Rheumatoid factors (RFs) are polyreactive antibodies that can bind disease-specific epitopes. Recent studies have found that RFs in COVID-19 can bind novel IgG epitopes, which provides new insights into the mechanism of RFs.
JOURNAL OF AUTOIMMUNITY
(2024)
Article
Immunology
Johanne Liberatore, Yann Nguyen, Jerome Hadjadj, Pascal Cohen, Luc Mouthon, Xavier Puechal, Loic Guillevin, Benjamin Terrier
Summary: B-cell depletion induced by rituximab (RTX) in ANCA-associated vasculitis (AAV) can lead to decreased gammaglobulin levels, which is associated with an increased risk of relapse and severe infections. Older age, low gammaglobulin levels, and receiving pulses of methylprednisolone at induction therapy are risk factors for gammaglobulin decline.
JOURNAL OF AUTOIMMUNITY
(2024)