scholarly journals MECHANISMS IN ENDOCRINOLOGY: Insulin and type 1 diabetes: immune connections

2013 ◽  
Vol 168 (2) ◽  
pp. R19-R31 ◽  
Author(s):  
Sloboda Culina ◽  
Vedran Brezar ◽  
Roberto Mallone
Keyword(s):  
T Cells ◽  
Type 1 Diabetes ◽  
Immune Responses ◽  
Current Knowledge ◽  
Target Antigen ◽  
Β Cells ◽  
Autoreactive T Cells ◽  
Central Tolerance ◽  
Initial Target

Insulin is the hormone produced by pancreatic β-cells, with a central role in carbohydrate and fat metabolism. Together with its precursors preproinsulin and proinsulin, insulin is also a key target antigen (Ag) of the autoimmune islet destruction leading to type 1 diabetes. Being recognized by both autoantibodies (aAbs) and autoreactive T cells, insulin plays a triggering role, at least in rodent models, in diabetes pathogenesis. It is expressed not only by β-cells but also in the thymus, where it plays a major role in central tolerance mechanisms. We will summarize current knowledge concerning insulin, its role in β-cell autoimmunity as initial target Ag, its recognition by aAbs and autoreactive T cells, and the detection of these immune responses to provide biomarkers for clinical trials employing insulin as an immune modulatory agent.

scholarly journals Inherent ER stress in pancreatic islet β cells causes self-recognition by autoreactive T cells in type 1 diabetes

2016 ◽  
Vol 72 ◽  
pp. 33-46 ◽  
Author(s):  
Meghan L. Marré ◽  
Jennifer L. Profozich ◽  
Jorge T. Coneybeer ◽  
Xuehui Geng ◽  
Suzanne Bertera ◽  
...  
Keyword(s):  
T Cells ◽  
Type 1 Diabetes ◽  
Er Stress ◽  
Pancreatic Islet ◽  
Β Cells ◽  
Autoreactive T Cells ◽  
Self Recognition

scholarly journals Thymic B Cells as a New Player in the Type 1 Diabetes Response

2021 ◽  
Vol 12 ◽  
Author(s):  
Richard B. Greaves ◽  
Dawei Chen ◽  
E. Allison Green
Keyword(s):  
T Cells ◽  
Type 1 Diabetes ◽  
B Cells ◽  
Small Population ◽  
Thymic Epithelial Cells ◽  
Lymphoid Tissues ◽  
Autoreactive T Cells ◽  
Central Tolerance ◽  
Autoimmune Conditions

Type 1 diabetes (T1d) results from a sustained autoreactive T and B cell response towards insulin-producing β cells in the islets of Langerhans. The autoreactive nature of the condition has led to many investigations addressing the genetic or cellular changes in primary lymphoid tissues that impairs central tolerance- a key process in the deletion of autoreactive T and B cells during their development. For T cells, these studies have largely focused on medullary thymic epithelial cells (mTECs) critical for the effective negative selection of autoreactive T cells in the thymus. Recently, a new cellular player that impacts positively or negatively on the deletion of autoreactive T cells during their development has come to light, thymic B cells. Normally a small population within the thymus of mouse and man, thymic B cells expand in T1d as well as other autoimmune conditions, reside in thymic ectopic germinal centres and secrete autoantibodies that bind selective mTECs precipitating mTEC death. In this review we will discuss the ontogeny, characteristics and functionality of thymic B cells in healthy and autoimmune settings. Furthermore, we explore how in silico approaches may help decipher the complex cellular interplay of thymic B cells with other cells within the thymic microenvironment leading to new avenues for therapeutic intervention.

scholarly journals Nonlinear Analysis for a Type-1 Diabetes Model with Focus on T-Cells and Pancreatic β-Cells Behavior

2020 ◽  
Vol 25 (2) ◽  
pp. 23
Author(s):  
Diana Gamboa ◽  
Carlos E. Vázquez ◽  
Paul J. Campos
Keyword(s):  
T Cells ◽  
Type 1 Diabetes ◽  
Cell Population ◽  
Closed Loop ◽  
Pancreatic Β Cell ◽  
Activated Macrophages ◽  
Β Cells ◽  
Β Cell ◽  
Pancreatic Β Cells

Type-1 diabetes mellitus (T1DM) is an autoimmune disease that has an impact on mortality due to the destruction of insulin-producing pancreatic β -cells in the islets of Langerhans. Over the past few years, the interest in analyzing this type of disease, either in a biological or mathematical sense, has relied on the search for a treatment that guarantees full control of glucose levels. Mathematical models inspired by natural phenomena, are proposed under the prey–predator scheme. T1DM fits in this scheme due to the complicated relationship between pancreatic β -cell population growth and leukocyte population growth via the immune response. In this scenario, β -cells represent the prey, and leukocytes the predator. This paper studies the global dynamics of T1DM reported by Magombedze et al. in 2010. This model describes the interaction of resting macrophages, activated macrophages, antigen cells, autolytic T-cells, and β -cells. Therefore, the localization of compact invariant sets is applied to provide a bounded positive invariant domain in which one can ensure that once the dynamics of the T1DM enter into this domain, they will remain bounded with a maximum and minimum value. Furthermore, we analyzed this model in a closed-loop scenario based on nonlinear control theory, and proposed bases for possible control inputs, complementing the model with them. These entries are based on the existing relationship between cell–cell interaction and the role that they play in the unchaining of a diabetic condition. The closed-loop analysis aims to give a deeper understanding of the impact of autolytic T-cells and the nature of the β -cell population interaction with the innate immune system response. This analysis strengthens the proposal, providing a system free of this illness—that is, a condition wherein the pancreatic β -cell population holds and there are no antigen cells labeled by the activated macrophages.

scholarly journals Evidence for In Vivo Primed and Expanded Autoreactive T Cells as a Specific Feature of Patients with Type 1 Diabetes

2007 ◽  
Vol 179 (9) ◽  
pp. 5785-5792 ◽  
Author(s):  
Paolo Monti ◽  
Miriam Scirpoli ◽  
Andrea Rigamonti ◽  
Anya Mayr ◽  
Annika Jaeger ◽  
...  
Keyword(s):  
T Cells ◽  
Type 1 Diabetes ◽  
Autoreactive T Cells

scholarly journals Variation in the CTLA4 3′UTR has phenotypic consequences for autoreactive T cells and associates with genetic risk for type 1 diabetes

2015 ◽  
Vol 17 (1) ◽  
pp. 75-78 ◽  
Author(s):  
V M de Jong ◽  
A Zaldumbide ◽  
A R van der Slik ◽  
S Laban ◽  
B P C Koeleman ◽  
...  
Keyword(s):  
T Cells ◽  
Type 1 Diabetes ◽  
Genetic Risk ◽  
Autoreactive T Cells

scholarly journals Probiotics and Prebiotics for the Amelioration of Type 1 Diabetes: Present and Future Perspectives

2019 ◽  
Vol 7 (3) ◽  
pp. 67 ◽  
Author(s):  
Sidharth Mishra ◽  
Shaohua Wang ◽  
Ravinder Nagpal ◽  
Brandi Miller ◽  
Ria Singh ◽  
...  
Keyword(s):  
T Cells ◽  
Type 1 Diabetes ◽  
Immune System ◽  
Gut Microbiota ◽  
Adaptive Immune Response ◽  
Early Years ◽  
Autoimmune Response ◽  
Β Cells ◽  
Environmental Interactions

Type 1-diabetes (T1D) is an autoimmune disease characterized by immune-mediated destruction of pancreatic beta (β)-cells. Genetic and environmental interactions play an important role in immune system malfunction by priming an aggressive adaptive immune response against β-cells. The microbes inhabiting the human intestine closely interact with the enteric mucosal immune system. Gut microbiota colonization and immune system maturation occur in parallel during early years of life; hence, perturbations in the gut microbiota can impair the functions of immune cells and vice-versa. Abnormal gut microbiota perturbations (dysbiosis) are often detected in T1D subjects, particularly those diagnosed as multiple-autoantibody-positive as a result of an aggressive and adverse immunoresponse. The pathogenesis of T1D involves activation of self-reactive T-cells, resulting in the destruction of β-cells by CD8+ T-lymphocytes. It is also becoming clear that gut microbes interact closely with T-cells. The amelioration of gut dysbiosis using specific probiotics and prebiotics has been found to be associated with decline in the autoimmune response (with diminished inflammation) and gut integrity (through increased expression of tight-junction proteins in the intestinal epithelium). This review discusses the potential interactions between gut microbiota and immune mechanisms that are involved in the progression of T1D and contemplates the potential effects and prospects of gut microbiota modulators, including probiotic and prebiotic interventions, in the amelioration of T1D pathology, in both human and animal models.

scholarly journals Expression of the B7.1 Costimulatory Molecule on Pancreatic β Cells Abrogates the Requirement for CD4 T Cells in the Development of Type 1 Diabetes

2004 ◽  
Vol 173 (2) ◽  
pp. 787-796 ◽  
Author(s):  
Evis Havari ◽  
Ana Maria Lennon-Dumenil ◽  
Ludger Klein ◽  
Devon Neely ◽  
Jacqueline A. Taylor ◽  
...  
Keyword(s):  
T Cells ◽  
Type 1 Diabetes ◽  
Cd4 T Cells ◽  
Costimulatory Molecule ◽  
Β Cells ◽  
Pancreatic Β Cells

scholarly journals Extending Remission and Reversing New-Onset Type 1 Diabetes by Targeted Ablation of Autoreactive T Cells

Diabetes ◽  
2018 ◽  
Vol 67 (11) ◽  
pp. 2319-2328
Author(s):  
Kaitlin R. Carroll ◽  
Eileen E. Elfers ◽  
Joseph J. Stevens ◽  
Jonathan P. McNally ◽  
David A. Hildeman ◽  
...  
Keyword(s):  
T Cells ◽  
Type 1 Diabetes ◽  
Autoreactive T Cells ◽  
Onset Type ◽  
New Onset
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