scholarly journals Altered Frequency and Phenotype of HLA-G-Expressing DC-10 in Type 1 Diabetes Patients at Onset and in Subjects at Risk to Develop the Disease

2021 ◽  
Vol 12 ◽  
Author(s):  
Giada Amodio ◽  
Alessandra Mandelli ◽  
Rosalia Curto ◽  
Paola M. V. Rancoita ◽  
Angela Stabilini ◽  
...  
Keyword(s):  
At Risk ◽  
Type 1 Diabetes ◽  
Peripheral Blood ◽  
Low Frequency ◽  
Β Cells ◽  
Factors Affecting ◽  
Low Levels ◽  
Antigen Presenting ◽  
Chronic Autoimmune Disease

Type 1 diabetes (T1D) is a chronic autoimmune disease resulting in progressive destruction of β-cells. Several factors affecting lymphocyte and antigen-presenting cells, including dendritic cells (DCs), contribute to defective maintenance of tolerance in T1D. DC-10 are a subset of human DCs involved in IL-10-mediated tolerance. A precise monitoring of DC-10 in the peripheral blood is possible thanks to the discovery of specific biomarkers. DC-10, being cells that naturally express HLA-G, may be used for the appropriate staging of the disease. By enumerating and phenotypically characterizing DC-10 in the peripheral blood of subjects at different stages of T1D development—first-degree relatives (FDRs) of T1D patients, without (Abneg) or with (Abpos) autoantibodies, T1D patients at onset, and age-matched healthy controls (HCs)—we showed that DC-10 contain a high proportion of HLA-G-expressing cells as compared with monocytes. We reported that a low frequency of DC-10 during disease development is paralleled with the increased proportion of pro-inflammatory cDC2 cells. Moreover, DC-10 number and phenotype differ from Abneg FDRs, Abpos FDRs, and T1D patients compared with HCs, and DC-10 from T1D patients express low levels of CD83. Finally, multiple regression analysis, considering DC-10 and HLA-G-related parameters, showed that Abneg FDRs are more similar to subjects with autoimmunity than to HCs. This is the first demonstration that impairment in DC-10 number and phenotype, specifically CD83 expression, is associated with risk of developing T1D, suggesting a possible use of CD83+ DC-10 to stratify individuals at risk of T1D in conjunction with classical prognostic factors.

Low Frequency of Regulatory T Cells in the Peripheral Blood of Children with Type 1 Diabetes Diagnosed under the Age of Five

2012 ◽  
Vol 60 (4) ◽  
pp. 307-313 ◽  
Author(s):  
Agnieszka Szypowska ◽  
Anna Stelmaszczyk-Emmel ◽  
Urszula Demkow ◽  
Włodzimierz Łuczyński
Keyword(s):  
T Cells ◽  
Type 1 Diabetes ◽  
Regulatory T Cells ◽  
Peripheral Blood ◽  
Low Frequency

Vitamin D and Omega-3 Polyunsaturated Fatty Acids in Type 1 Diabetes modulation

2022 ◽  
Vol 22 ◽  
Author(s):  
Thais Sibioni Berti Bastos ◽  
Tárcio Teodoro Braga ◽  
Mariana Rodrigues Davanso
Keyword(s):  
Fatty Acids ◽  
Vitamin D ◽  
Type 1 Diabetes ◽  
Polyunsaturated Fatty Acids ◽  
Immune Cell ◽  
Omega 3 ◽  
Β Cells ◽  
Potential Benefits ◽  
Chronic Autoimmune Disease

Background: Type 1 diabetes (T1D) is a chronic autoimmune disease that affects people globally. Usually developed during childhood, T1D is characterized by the destruction of pancreatic β-cells due to immune cell attack and the establishment of an inflammatory process. Objective: The study aimed to investigate the effects of vitamin D through its nuclear receptor and the ω-3 polyunsaturated fatty acids (PUFAs) through their lipid derivatives in T1D modulation. Both components exert anti-inflammatory activity and act directly on cells of the immune system, attenuating the destruction of insulin-producing cells. Furthermore, they lead to a better glycemic level, reducing the need for insulin and a normal immune state, such as C-peptide maintenance. Method: Presently, our review highlights the significant studies that evaluated the supplementation of vitamin D and ω-3 PUFAs in humans and animal models in the modulation of T1D. Conclusion: The data collected suggests that supplementation can provide potential benefits, mainly when done early in the diagnosis, since it reduces the need for insulin and the risk of complications generated by the disease.

scholarly journals A peripheral blood transcriptomic signature predicts autoantibody development in infants at risk of type 1 diabetes

JCI Insight ◽  
2018 ◽  
Vol 3 (5) ◽  
Author(s):  
Ahmed M. Mehdi ◽  
Emma E. Hamilton-Williams ◽  
Alexandre Cristino ◽  
Anette Ziegler ◽  
Ezio Bonifacio ◽  
...  
Keyword(s):  
At Risk ◽  
Type 1 Diabetes ◽  
Peripheral Blood ◽  
Transcriptomic Signature

Understanding the Immunology of Type 1 Diabetes – An Overview of Current Knowledge and Perspectives for the Future

2010 ◽  
Vol 8 (2) ◽  
pp. 70
Author(s):  
Anil Piya ◽  
Aaron W Michels ◽  
◽  
Keyword(s):  
Type 1 Diabetes ◽  
Disease Risk ◽  
Current Knowledge ◽  
Immune Intervention ◽  
Β Cells ◽  
Beta Cell Destruction ◽  
Chronic Autoimmune Disease ◽  
Ultimate Cure

Type 1 diabetes is a chronic autoimmune disease resulting from the immune destruction of insulin-producing β-cells in pancreatic islets. It is now a predicable disease in humans with the measurement of islet autoantibodies. Despite the ability to assess disease risk, there is no cure for type 1 diabetes and treatment requires lifelong insulin administration. Individuals with type 1 diabetes are at risk of long-term complications of the disease and the development of concomitant autoimmune disorders. Our understanding of the immunology of diabetes has increased greatly over the last decade at a basic science level, with translation to type 1 diabetes patients. Therapies are emerging to prevent beta cell destruction in these patients. This article centres around our current understanding of the immunology of type 1 diabetes, with a focus on immune intervention for the prevention and ultimate cure of the disease.

scholarly journals Physiological β Cell Death Triggers Priming of Self-reactive T Cells by Dendritic Cells in a Type-1 Diabetes Model

2003 ◽  
Vol 198 (10) ◽  
pp. 1527-1537 ◽  
Author(s):  
Shannon Turley ◽  
Laurent Poirot ◽  
Masakazu Hattori ◽  
Christophe Benoist ◽  
Diane Mathis
Keyword(s):  
Cell Death ◽  
Type 1 Diabetes ◽  
Nod Mice ◽  
Mouse Strains ◽  
Β Cells ◽  
Β Cell ◽  
Diabetes Model ◽  
Pancreatic Lymph Nodes ◽  
Antigen Presenting

The prelude to type-1 diabetes is leukocyte infiltration into the pancreatic islets, or insulitis. This process begins in pancreatic lymph nodes when T lymphocytes reactive to islet β cells encounter antigen-presenting cells (APCs) displaying peptides derived from β cell proteins. We show here that a ripple of physiological β cell death, which occurs at 2 wk of age in all mouse strains, precipitates the arrival of such APCs, and that the relevant APC is a dendritic cell of CD11c+CD11b+CD8α− phenotype. These findings have significant implications concerning the nature of the diabetes-provoking deficits in NOD mice, the identity of the primordial diabetogenic antigens, and our understanding of the balance between immunity and tolerance in a pathological context.

scholarly journals NK Cells and Type 1 Diabetes

2006 ◽  
Vol 13 (2-4) ◽  
pp. 101-107 ◽  
Author(s):  
Melanie Rodacki ◽  
Adolpho Milech ◽  
José Egídio Paulo de Oliveira
Keyword(s):  
T Cells ◽  
Type 1 Diabetes ◽  
Nk Cells ◽  
Target Cells ◽  
Β Cells ◽  
Pancreatic Β Cells ◽  
Immune Mediated ◽  
Antigen Presenting

Type 1 diabetes (T1D) is characterized by an immuno-mediated progressive destruction of the pancreatic β cells. Due to the ability of NK cells to kill target cells as well as to interact with antigen-presenting and T cells, it has been suggested that they could be involved in one or multiple steps of the immune-mediated attack that leads to T1D. Abnormalities in the frequency and activity of NK cells have been described both in animal models and patients with T1D. Some of these alterations are linked to its onset while others seem to be a consequence of the disease. Here, we discuss the main characteristics of NK cells and review the studies that investigated the role of NK cells in T1D, both in mouse models and humans.

GAD65- and proinsulin-specific CD4+ T-cells detected by MHC class II tetramers in peripheral blood of type 1 diabetes patients and at-risk subjects

2005 ◽  
Vol 25 (3) ◽  
pp. 235-243 ◽  
Author(s):  
Viveka Öling ◽  
Jane Marttila ◽  
Jorma Ilonen ◽  
William W. Kwok ◽  
Gerald Nepom ◽  
...  
Keyword(s):  
At Risk ◽  
T Cells ◽  
Type 1 Diabetes ◽  
Mhc Class Ii ◽  
Peripheral Blood ◽  
Cd4 T Cells ◽  
Class Ii ◽  
Diabetes Patients

scholarly journals The type 1 diabetes at-risk allele at rs3842753 associates with increased beta cell INS mRNA in a meta-analysis of single cell RNA sequencing data

2020 ◽  
Author(s):  
Su Wang ◽  
Stephane Flibotte ◽  
Joan Camunas-Soler ◽  
Patrick E. MacDonald ◽  
James D. Johnson
Keyword(s):  
Gene Expression ◽  
At Risk ◽  
Type 1 Diabetes ◽  
Er Stress ◽  
Single Cell ◽  
Beta Cells ◽  
Risk Allele ◽  
Β Cells

ABSTRACTType 1 diabetes is characterized by the autoimmune destruction of insulin secreting beta-cells. Genetic variations upstream at the insulin (INS) locus contribute to ~10% of type 1 diabetes heritable risk. Multiple studies showed an association between rs3842753 C/C genotype and type 1 diabetes susceptibility. Three small studies have reported an association between the rs3842753 C allele and increased whole pancreas INS expression. To date, no large-scale studies have looked at the effect of those genetic variations on insulin expression at the single cell level. We aligned all human islet single cell RNA sequencing datasets available to us in 2020 to the reference genome GRCh38.98 and genotyped rs3842753. We integrated 2315 beta-cells from 13 A/A donors, 23 A/C heterozygous donors, and 35 C/C at-risk donors. The donors included adults without diabetes and with type 2 diabetes. INS expression mean and variance were significantly higher in single β cells from females compared with males. Comparing across all β cells, we found that rs3842753 C containing cells (either homozygous or heterozygous) had the highest INS expression. We also found that β cells with the rs3842753 C allele had significantly higher ER stress marker gene expression compared to the A/A homozygous genotype. These findings support the emerging concept that inherited risk of type 1 diabetes may be associated with elevated insulin production at the mRNA level which may lead to β cell ER stress and fragility.KEY MESSAGESThe type 1 diabetes at risk allele at rs3842753 is associated with increased INS gene expression and ER stress in single human beta-cells.Single beta-cells from female donors and donors with type 2 diabetes exhibit a wider range of INS gene expression.

scholarly journals Is It Time to Screen the General Population for Type 1 Diabetes?

2015 ◽  
Vol 11 (01) ◽  
pp. 10 ◽  
Author(s):  
Kimber M Simmons ◽  
Aaron W Michels ◽  
◽  
Keyword(s):  
Type 1 Diabetes ◽  
General Population ◽  
Genetic Risk ◽  
Population Screening ◽  
Β Cells ◽  
Β Cell ◽  
Targeted Screening ◽  
History Of ◽  
Chronic Autoimmune Disease

Type 1 diabetes (T1D) is a chronic autoimmune disease characterized by destruction of insulin-producing β cells in the pancreas. The incidence of T1D is increasing dramatically, and the prevalence has doubled in the last 2 decades, further increasing the morbidity and mortality associated with the disease. T1D is now predictable with the measurement of antibodies directed against β cell proteins. Islet autoantibodies (IAs) are detectable from the peripheral blood months to years before clinical diagnosis. With the presence of two or more antibodies, the risk for developing T1D is nearly 100 % given enough time. Targeted screening for T1D risk has been carried out in first-degree relatives and those with a significant genetic risk. However, more than 85 % of individuals who are diagnosed with T1D do not have a family history. In light of the predictability of T1D and recent advances in IA measurement, general population screening is on the horizon. We provide an overview of the history of general population screening and discuss the rationale for and arguments against screening the general population for T1D risk.

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