Article
Multidisciplinary Sciences
Joshua M. Gammon, Sean T. Carey, Vikas Saxena, Haleigh B. Eppler, Shannon J. J. Tsai, Christina Paluskievicz, Yanbao Xiong, Lushen Li, Marian Ackun-Farmmer, Lisa H. Tostanoski, Emily A. Gosselin, Alexis A. Yanes, Xiangbin Zeng, Robert S. Oakes, Jonathan S. Bromberg, Christopher M. Jewell
Summary: The authors have successfully promoted the production of antigen-specific regulatory T cells and prevented the occurrence of type 1 diabetes and allogenic islet transplantation by delivering immune signals to lymph nodes. Antigen-specific tolerance is an important goal in experimental immunotherapy for autoimmune diseases and organ transplantation, as it can selectively inhibit harmful immune responses without compromising protective immunity. However, the current challenge lies in the ineffective control over immune signal targeting, which limits the efficacy and causes non-specific suppression.
NATURE COMMUNICATIONS
(2023)
Review
Endocrinology & Metabolism
Leonard C. Harrison
Summary: Insulin, as a 'cure' for type 1 diabetes, may also be a potential 'cause'. Autoimmunity to insulin could be an early marker of risk for type 1 diabetes in young children. Research in NOD mouse models suggests that (pro)insulin plays a critical role in driving beta cell pathology.
MOLECULAR METABOLISM
(2021)
Review
Biochemistry & Molecular Biology
Jamie L. Felton, Holly Conway, Rachel H. Bonami
Summary: Islet autoantibodies are key biomarkers for predicting T1D risk, signaling immune tolerance breach by B lymphocytes. Strategies to prevent T1D development may involve eliminating T and B cells or disrupting T cell interactions, but global immune cell disruption poses risks, hence the focus on antigen-specific therapy for T1D prevention.
Article
Cell Biology
Soo Jung Yang, Akhilesh K. Singh, Travis Drow, Tori Tappen, Yuchi Honaker, Fariba Barahmand-Pour-Whitman, Peter S. Linsley, Karen Cerosaletti, Kelsey Mauk, Yufei Xiang, Jessica Smith, Emma Mortensen, Peter J. Cook, Karen Sommer, Iram Khan, Denny Liggitt, David J. Rawlings, Jane H. Buckner
Summary: The adoptive transfer of engineered T-regs (EngT(regs)) specific to islet antigens shows therapeutic potential in preventing type 1 diabetes by suppressing both effector T cells recognizing the same islet antigen and bystander effector T cells. EngT(regs) can home to the pancreas and block diabetes triggered by specific or polyclonal effector T cells. This approach demonstrates the promise of antigen-specific EngT(regs) as a targeted therapy for T1D.
SCIENCE TRANSLATIONAL MEDICINE
(2022)
Review
Biochemistry & Molecular Biology
Xuejiao Zhang, Ying Dong, Dianyuan Liu, Liu Yang, Jiayi Xu, Qing Wang
Summary: Type 1 diabetes mellitus is an autoimmune disease caused by the destruction of pancreatic beta cells. Immune regulation with pancreatic islet auto-antigens is a specific and safe treatment for T1DM. Early screening of autoantibodies can help identify high-risk individuals and prevent T1DM. Inducing self-tolerance in pre-diabetic patients can also slow down autoimmunity and achieve secondary prevention.
JOURNAL OF TRACE ELEMENTS IN MEDICINE AND BIOLOGY
(2022)
Article
Virology
William A. Langley, Andreas Wieland, Hasan Ahmed, Mohammed Ata ur Rasheed, Carl W. Davis, Jaturong Sewatanon, Scott N. Mueller, Mark J. Shlomchik, Veronika I. Zarnitsyna, Rustom Antia, Rafi Ahmed
Summary: Virus-specific antibodies play a crucial role in defending against reinfection. Plasma cells in the bone marrow secrete antibodies continuously, maintaining serum antibody levels even without antigen presence. This study demonstrates that virus-specific plasma cells exhibit intrinsic longevity and can maintain stable antibody levels in the absence of memory B cells, providing insights into plasma cell longevity and implications for vaccination.
JOURNAL OF VIROLOGY
(2022)
Article
Immunology
Ranjeny Thomas, Jose M. Carballido, Johnna D. Wesley, Simi T. Ahmed
Summary: Antigen-specific immunotherapy shows promise for treating type 1 diabetes, but faces obstacles in clinical translation. The key to overcoming these challenges lies in collaboration and cooperation among various stakeholders.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Immunology
Joseph R. Podojil, Samantha Genardi, Ming-Yi Chiang, Sandeep Kakade, Tobias Neef, Tushar Murthy, Michael T. Boyne, Adam Elhofy, Stephen D. Miller
Summary: Type 1 diabetes is an autoimmune disease that can be effectively inhibited by encapsulating multiple diabetogenic proteins in nanoparticles, which induce regulatory T cells and decrease inflammation in pancreatic islets.
JOURNAL OF IMMUNOLOGY
(2022)
Article
Immunology
Meng Li, Arata Itoh, Jingchao Xi, Chunsong Yu, Yuehong Wu, William M. Ridgway, Haipeng Liu
Summary: Efforts to restore immune tolerance to self-antigens without global immune suppression in autoimmune disorders have largely failed. However, modifying peptides with lipophilic compounds significantly enhances antigen presentation and induces immune tolerance, showing promise for the treatment of autoimmune diseases.
JOURNAL OF IMMUNOLOGY
(2021)
Review
Endocrinology & Metabolism
Eddie A. James, Alok V. Joglekar, Amelia K. Linnemann, Holger A. Russ, Sally C. Kent
Summary: In this article, the authors discuss the interface between islet beta cells and immune infiltrates, with a focus on T cells, in the context of T1D. They emphasize the importance of studying pancreatic and immune cell phenotypes and their impact on cell function to gain a comprehensive understanding of T1D disease etiology in humans. They also highlight the active role of beta cells and the critical axis of the T cell-beta cell interface in autoimmune responses.
MOLECULAR METABOLISM
(2023)
Article
Immunology
Sara Puente-Marin, Fabricia Dietrich, Peter Achenbach, Hugo Barcenilla, Johnny Ludvigsson, Rosaura Casas
Summary: GAD-alum injections into lymph nodes had a positive effect on T1D patients with DR3DQ2 haplotype, showing better preservation of C-peptide. Patients receiving GAD-alum had higher levels of GADA, GADA subclasses, GAD(65)-induced proliferation, and cytokine secretion compared to the placebo group. Good responders with DR3DQ2 haplotype had a distinct cellular immune response to GAD-alum injections, associated with increased IL13 secretion and proliferation.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Cell Biology
Shukkur M. Farooq, Hossam M. Ashour
Summary: The study demonstrates that CII-specific ACAID B cells can induce peripheral tolerance, and the adoptively transferred B cells have the ability to suppress immune responses after challenges with CII. This effect was replicated in multiple strains of mice, indicating potential therapeutic implications for the treatment of CII-mediated autoimmune diseases.
Article
Immunology
Colin J. Raposo, Judith D. Cserny, Gloria Serena, Jonathan N. Chow, Patricia Cho, Hanyang Liu, David Kotler, Armon Sharei, Howard Bernstein, Shinu John
Summary: Antigen-specific therapies using red blood cells as carriers have shown promising results in inducing immunotolerance towards self and foreign antigens, making them a potential treatment option for autoimmune diseases such as type 1 diabetes.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Immunology
Shuyao Qiu, Xiangqian Luo, Lihua Mo, Shuang Zhang, Yun Liao, Li Guan, Liteng Yang, Qinmiao Huang, Dabo Liu, Pingchang Yang
Summary: This study aims to enhance the therapeutic efficacy of allergen-specific immunotherapy (AIT) in experimental allergic rhinitis (AR) by using TAFA4 as an adjuvant. The results show that TAFA4 activates dendritic cells (DCs) in the airway tissues and induces the expression of IL-10, which attenuates the allergic response in mice.
Review
Endocrinology & Metabolism
Shivani K. Patel, Cindy S. Ma, Spiros Fourlanos, Jerry R. Greenfield
Summary: Studying autoantibody-negative T1D reveals the challenges and limitations in understanding this group, as they are excluded from immunomodulatory trials, hindering improvements in diagnostics and therapies for the disease.
TRENDS IN ENDOCRINOLOGY AND METABOLISM
(2021)
Article
Hematology
Jahnavi Aluri, Alicia Bach, Saara Kaviany, Luana Chiquetto Paracatu, Maleewan Kitcharoensakkul, Magdalena A. Walkiewicz, Christopher D. Putnam, Marwan Shinawi, Nermina Saucier, Elise M. Rizzi, Michael T. Harmon, Molly P. Keppel, Michelle Ritter, Morgan Similuk, Elaine Kulm, Michael Joyce, Adriana A. de Jesus, Raphaela Goldbach-Mansky, Yi-Shan Lee, Marina Cella, Peggy L. Kendall, Mary C. Dinauer, Jeffrey J. Bednarski, Christina Bemrich-Stolz, Scott W. Canna, Shirley M. Abraham, Matthew M. Demczko, Jonathan Powell, Stacie M. Jones, Amy M. Scurlock, Suk See De Ravin, Jack J. Bleesing, James A. Connelly, V. Koneti Rao, Laura G. Schuettpelz, Megan A. Cooper
Summary: Inborn errors of immunity (IEI) are genetically heterogeneous disorders with a wide clinical spectrum. A new study identified gain-of-function variants in the X-linked gene TLR8 as a novel molecular mechanism leading to this disease.
Review
Biochemistry & Molecular Biology
Jamie L. Felton, Holly Conway, Rachel H. Bonami
Summary: Islet autoantibodies are key biomarkers for predicting T1D risk, signaling immune tolerance breach by B lymphocytes. Strategies to prevent T1D development may involve eliminating T and B cells or disrupting T cell interactions, but global immune cell disruption poses risks, hence the focus on antigen-specific therapy for T1D prevention.
Article
Biochemistry & Molecular Biology
James D. West, Eric D. Austin, Elise M. Rizzi, Ling Yan, Harikrishna Tanjore, Amber L. Crabtree, Christy S. Moore, Gladson Muthian, Erica J. Carrier, David A. Jacobson, Rizwan Hamid, Peggy L. Kendall, Susan Majka, Anandharajan Rathinasabapathy
Summary: Loss of function KCNK3 mutation alters various physiological processes through inflammation, affecting factors such as inflammation and metabolism in response to hypoxia, dysregulation of bone marrow cells, and the role of inflammation in driving pulmonary arterial hypertension (PAH). Studies on both animal models and human samples suggest that altered circulating immune cells may play a key role in driving PAH susceptibility in patients with KCNK3 mutation.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Medicine, Research & Experimental
Erin M. Wilfong, Katherine N. Vowell, Kaitlyn E. Bunn, Elise Rizzi, Narender Annapureddy, Rosemarie B. Dudenhofer, April Barnado, Rachel H. Bonami, Joyce E. Johnson, Leslie J. Crofford, Peggy L. Kendall
Summary: This study found that CD21(lo/neg) cells are significantly increased in systemic sclerosis patients with interstitial lung disease, indicating a potential biomarker for this condition.
CLINICAL AND EXPERIMENTAL MEDICINE
(2022)
Article
Immunology
Lindsay E. Nyhoff, Amber S. Griffith, Emily S. Clark, James W. Thomas, Wasif N. Khan, Peggy L. Kendall
Summary: Bruton's tyrosine kinase (Btk) plays a crucial role in inhibiting the development of mature anti-insulin B cells, removal of Btk affects the functions of anti-insulin B cells in terms of protein expression, proliferation, etc.
JOURNAL OF IMMUNOLOGY
(2021)
Article
Immunology
Erin M. Wilfong, Todd Bartkowiak, Katherine N. Vowell, Camille S. Westlake, Jonathan M. Irish, Peggy L. Kendall, Leslie J. Crofford, Rachel H. Bonami
Summary: This study identifies two distinct immune endotypes in patients with idiopathic inflammatory myopathies and reveals shared immunologic features among all patients, despite different clinical features.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Ana P. M. Serezani, Bruno D. Pascoalino, Julia M. R. Bazzano, Katherine N. Vowell, Harikrishna Tanjore, Chase J. Taylor, Carla L. Calvi, A. Scott McCall, Matthew D. Bacchetta, Ciara M. Shaver, Lorraine B. Ware, Margaret L. Salisbury, Nicholas E. Banovich, Peggy L. Kendall, Jonathan A. Kropski, Timothy S. Blackwell
Summary: By studying immune cell subsets and transcriptional profiles, this research reveals increased and activated immune cells in the lungs of IPF patients, indicating the importance of IFN-γ signaling and adaptive immunity in the pathogenesis of IPF.
AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY
(2022)
Article
Immunology
Rachel H. Bonami, Christina E. Thurman, Sonam Verma, Camille S. Westlake, Lindsay E. Nyhoff, Bridgette B. Barron, Andrea Reboldi, Peggy L. Kendall
Summary: This study reveals that BTK is crucial for maintaining normal intestinal IgA development and the IgA coating of commensal bacteria. Deficiency in BTK leads to decreased IgA levels in the small intestines and a shift in the composition of IgA-coated microbes.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Multidisciplinary Sciences
Kevin J. Kramer, Erin M. Wilfong, Kelsey Voss, Sierra M. Barone, Andrea R. Shiakolas, Nagarajan Raju, Caroline E. Roe, Naveenchandra Suryadevara, Lauren M. Walker, Steven C. Wall, Ariana Paulo, Samuel Schaefer, Debolanle Dahunsi, Camille S. Westlake, James E. Crowe, Robert H. Carnahan, Jeffrey C. Rathmell, Rachel H. Bonami, Ivelin S. Georgiev, Jonathan M. Irish
Summary: Through the analysis of multiple single-cell technologies, researchers have identified antigen-specific cells and antibody responses to the RNA vaccine BNT162b2, which is crucial for understanding the immune mechanisms of RNA vaccines.
NATURE COMMUNICATIONS
(2022)
Article
Biochemical Research Methods
Erin M. Wilfong, Katherine N. Vowell, Leslie J. Crofford, Peggy L. Kendall
Summary: This study used multiparameter flow cytometry and tSNE algorithm to analyze B cells from healthy participants, revealing significant phenotypic overlap between autoreactive and normal activated B cells, and identifying multiple subpopulations of CD19(+)CD21(lo) B cells.
Meeting Abstract
Rheumatology
Erin Wilfong, Leslie Crofford, Rachel Bonami
ARTHRITIS & RHEUMATOLOGY
(2022)
Meeting Abstract
Rheumatology
Erin Wilfong, Alberto Cisneros, Jennifer Young--Glazer, Scott Smith, Leslie Crofford, Rachel Bonami
ARTHRITIS & RHEUMATOLOGY
(2021)
Meeting Abstract
Rheumatology
Erin Wilfong, Todd Bartkowiak, Katherine Vowell, Camille Westlake, Jonathan Irish, Peggy Kendall, Leslie Crofford, Rachel Bonami
ARTHRITIS & RHEUMATOLOGY
(2021)