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Article ; Online: Self-Antigens Targeted by Regulatory T Cells in Type 1 Diabetes.

Mitchell, Angela M / Michels, Aaron W

International journal of molecular sciences

2022 Volume 23, Issue 6

Abstract: While progress has been made toward understanding mechanisms that lead to the development of autoimmunity, there is less knowledge regarding protective mechanisms from developing such diseases. For example, in type 1 diabetes (T1D), the immune-mediated ... ...

Abstract	While progress has been made toward understanding mechanisms that lead to the development of autoimmunity, there is less knowledge regarding protective mechanisms from developing such diseases. For example, in type 1 diabetes (T1D), the immune-mediated form of diabetes, the role of pathogenic T cells in the destruction of pancreatic islets is well characterized, but immune-mediated mechanisms that contribute to T1D protection have not been fully elucidated. One potential protective mechanism includes the suppression of immune responses by regulatory CD4 T cells (Tregs) that recognize self-peptides from islets presented by human leukocyte antigen (HLA) class II molecules. In this review, we summarize what is known about the antigenic self-peptides recognized by Tregs in the context of T1D.
MeSH term(s)	Autoantigens ; Autoimmunity ; Diabetes Mellitus, Type 1/pathology ; HLA Antigens ; Humans ; Islets of Langerhans/pathology ; T-Lymphocytes, Regulatory
Chemical Substances	Autoantigens ; HLA Antigens
Language	English
Publishing date	2022-03-15
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms23063155
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Implementation of a minimally invasive cell culture system to measure the regulation of inflammation in a school-based sample of adolescents.

McDade, Thomas W / Giletta, Matteo / Miller, Aaron A / Krause, Keegan C / Michels, Nathalie

American journal of human biology : the official journal of the Human Biology Council

2024 , Page(s) e24077

Abstract: Dysregulated inflammation underlies many human diseases, and measures of responsiveness to activation, and sensitivity to inhibition, provide important information beyond baseline assessments of chronic inflammation. This study implements a simplified ... ...

Abstract	Dysregulated inflammation underlies many human diseases, and measures of responsiveness to activation, and sensitivity to inhibition, provide important information beyond baseline assessments of chronic inflammation. This study implements a simplified cell culture protocol in a school-based setting, using finger stick capillary blood collected from 333 adolescents (age 11.4-15.6 years) incubated with lipopolysaccharide (LPS). Median cytokine responses for IL6, IL1β, and TNFα were 61.9, 26.2, and 11.2 pg/mL, respectively. Samples were also incubated with LPS and glucocorticoid (GC) to measure GC sensitivity. Median responses were reduced in the presence of GC inhibition for IL6 (20.3 pg/mL), IL1β (10.5 pg/mL), and TNFα (3.3 pg/mL). Minimally invasive cell culture protocols provide novel opportunities for measuring inflammatory phenotypes in a wide range of non-clinical settings.
Language	English
Publishing date	2024-03-27
Publishing country	United States
Document type	Journal Article
ZDB-ID	1025339-7
ISSN	1520-6300 ; 1042-0533
ISSN (online)	1520-6300
ISSN	1042-0533
DOI	10.1002/ajhb.24077
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Article ; Online: Using the T Cell Receptor as a Biomarker in Type 1 Diabetes.

Nakayama, Maki / Michels, Aaron W

Frontiers in immunology

2021 Volume 12, Page(s) 777788

Abstract: T cell receptors (TCRs) are unique markers that define antigen specificity for a given T cell. With the evolution of sequencing and computational analysis technologies, TCRs are now prime candidates for the development of next-generation non-cell based T ...

Abstract	T cell receptors (TCRs) are unique markers that define antigen specificity for a given T cell. With the evolution of sequencing and computational analysis technologies, TCRs are now prime candidates for the development of next-generation non-cell based T cell biomarkers, which provide a surrogate measure to assess the presence of antigen-specific T cells. Type 1 diabetes (T1D), the immune-mediated form of diabetes, is a prototypical organ specific autoimmune disease in which T cells play a pivotal role in targeting pancreatic insulin-producing beta cells. While the disease is now predictable by measuring autoantibodies in the peripheral blood directed to beta cell proteins, there is an urgent need to develop T cell markers that recapitulate T cell activity in the pancreas and can be a measure of disease activity. This review focuses on the potential and challenges of developing TCR biomarkers for T1D. We summarize current knowledge about TCR repertoires and clonotypes specific for T1D and discuss challenges that are unique for autoimmune diabetes. Ultimately, the integration of large TCR datasets produced from individuals with and without T1D along with computational 'big data' analysis will facilitate the development of TCRs as potentially powerful biomarkers in the development of T1D.
MeSH term(s)	Alleles ; Animals ; Biomarkers ; Diabetes Mellitus, Type 1/diagnosis ; Diabetes Mellitus, Type 1/etiology ; Diabetes Mellitus, Type 1/metabolism ; Diabetes Mellitus, Type 1/therapy ; Disease Susceptibility ; Epitopes/chemistry ; Epitopes/immunology ; Epitopes/metabolism ; Genetic Predisposition to Disease ; Genetic Variation ; Histocompatibility Antigens/genetics ; Histocompatibility Antigens/immunology ; Humans ; Islets of Langerhans/immunology ; Islets of Langerhans/metabolism ; Peptides/immunology ; Peptides/metabolism ; Protein Binding ; Receptors, Antigen, T-Cell/genetics ; Receptors, Antigen, T-Cell/immunology ; Receptors, Antigen, T-Cell/metabolism ; T-Lymphocytes/immunology ; T-Lymphocytes/metabolism
Chemical Substances	Biomarkers ; Epitopes ; Histocompatibility Antigens ; Peptides ; Receptors, Antigen, T-Cell
Language	English
Publishing date	2021-11-17
Publishing country	Switzerland
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	2606827-8
ISSN	1664-3224 ; 1664-3224
ISSN (online)	1664-3224
ISSN	1664-3224
DOI	10.3389/fimmu.2021.777788
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Article ; Online: Immune Checkpoint Inhibitor-Induced Type 1 Diabetes: An Underestimated Risk.

Akturk, Halis Kaan / Michels, Aaron W

Mayo Clinic proceedings

2020 Volume 95, Issue 3, Page(s) 614–615

MeSH term(s)	Antineoplastic Agents, Immunological ; Diabetes Mellitus, Type 1 ; Humans ; Nivolumab
Chemical Substances	Antineoplastic Agents, Immunological ; Nivolumab (31YO63LBSN)
Language	English
Publishing date	2020-04-23
Publishing country	England
Document type	Letter ; Comment
ZDB-ID	124027-4
ISSN	1942-5546 ; 0025-6196
ISSN (online)	1942-5546
ISSN	0025-6196
DOI	10.1016/j.mayocp.2019.12.009
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Article ; Online: Advances in Diabetes Treatment - Once-Weekly Insulin.

Gottlieb, Peter A / Michels, Aaron W

The New England journal of medicine

2020 Volume 383, Issue 22, Page(s) 2171–2172

MeSH term(s)	Diabetes Mellitus, Type 2/drug therapy ; Glucagon-Like Peptides ; Humans ; Hypoglycemic Agents/administration & dosage ; Insulin/administration & dosage ; Insulin, Regular, Human
Chemical Substances	Hypoglycemic Agents ; Insulin ; Insulin, Regular, Human ; Glucagon-Like Peptides (62340-29-8)
Language	English
Publishing date	2020-12-20
Publishing country	United States
Document type	Editorial ; Comment
ZDB-ID	207154-x
ISSN	1533-4406 ; 0028-4793
ISSN (online)	1533-4406
ISSN	0028-4793
DOI	10.1056/NEJMe2031596
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Article ; Online: The pathogenesis, natural history, and treatment of type 1 diabetes: time (thankfully) does not stand still.

Michels, Aaron W / Redondo, Maria J / Atkinson, Mark A

The lancet. Diabetes & endocrinology

2021 Volume 10, Issue 2, Page(s) 90–92

MeSH term(s)	Diabetes Mellitus, Type 1/etiology ; Diabetes Mellitus, Type 1/therapy ; Humans
Language	English
Publishing date	2021-12-21
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural
ISSN	2213-8595
ISSN (online)	2213-8595
DOI	10.1016/S2213-8587(21)00344-2
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Similar Time Course of Humoral Response to SARS-CoV-2 mRNA Vaccines in People With and Without Type 1 Diabetes.

Jia, Xiaofan / Dong, Fran / Pyle, Laura / Michels, Aaron W / Yu, Liping / Rewers, Marian

Diabetes technology & therapeutics

2023 Volume 25, Issue 7, Page(s) 492–496

Abstract: Objective: ...

Abstract	Objective:
MeSH term(s)	Adult ; Humans ; COVID-19 Vaccines ; Diabetes Mellitus, Type 1 ; BNT162 Vaccine ; 2019-nCoV Vaccine mRNA-1273 ; SARS-CoV-2 ; Prospective Studies ; COVID-19/prevention & control ; Breakthrough Infections ; mRNA Vaccines
Chemical Substances	COVID-19 Vaccines ; BNT162 Vaccine ; 2019-nCoV Vaccine mRNA-1273 (EPK39PL4R4) ; mRNA Vaccines
Language	English
Publishing date	2023-04-12
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	1452816-2
ISSN	1557-8593 ; 1520-9156
ISSN (online)	1557-8593
ISSN	1520-9156
DOI	10.1089/dia.2023.0016
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Zs.A 5269: Show issues

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Article ; Online: T cell receptor sequencing in autoimmunity.

Mitchell, Angela M / Michels, Aaron W

Journal of life sciences (Westlake Village, Calif.)

2020 Volume 2, Issue 4, Page(s) 38–58

Abstract: T cells are an integral component of the adaptive immune response via the recognition of peptides by the cell surface-expressed T cell receptor (TCR). Rearrangement of the TCR genes results in a highly polymorphic repertoire on the T cells within a given ...

Abstract	T cells are an integral component of the adaptive immune response via the recognition of peptides by the cell surface-expressed T cell receptor (TCR). Rearrangement of the TCR genes results in a highly polymorphic repertoire on the T cells within a given individual. Although the diverse repertoire is beneficial for immune responses to foreign pathogens, recognition of self-peptides by T cells can contribute to the development of autoimmune disorders. Increasing evidence supports a pathogenic role for T cells in autoimmune pathology, and it is of interest to determine the TCR repertoires involved in autoimmune disease development. In this review, we summarize methodologies and advancements in the TCR sequencing field and discuss recent studies focused on TCR sequencing in a variety of autoimmune conditions. The rapidly evolving methodology of TCR sequencing has the potential to allow for a better understanding of autoimmune disease pathogenesis, identify disease-specific biomarkers, and aid in developing therapies to prevent and treat a number of these disorders.
Language	English
Publishing date	2020-12-23
Publishing country	United States
Document type	Journal Article
ISSN	2688-1020
ISSN (online)	2688-1020
DOI	10.36069/jols/20201203
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Article ; Online: Adverse events associated with immune checkpoint inhibitors: a new era in autoimmune diabetes.

Akturk, Halis Kaan / Michels, Aaron W

Current opinion in endocrinology, diabetes, and obesity

2020 Volume 27, Issue 4, Page(s) 187–193

Abstract: Purpose of review: To summarize a new form of autoimmune diabetes as an adverse event of specific cancer immunotherapies. Immune checkpoint inhibitors are revolutionary treatments in advanced cancers; however, they can cause type 1 diabetes following ... ...

Abstract	Purpose of review: To summarize a new form of autoimmune diabetes as an adverse event of specific cancer immunotherapies. Immune checkpoint inhibitors are revolutionary treatments in advanced cancers; however, they can cause type 1 diabetes following treatment with these state-of-the-art therapies. Recent findings: A review of the literature showed that this new form of autoimmune diabetes has significant similarities with childhood-onset type 1 diabetes but also some distinctions. It frequently presents with severe diabetic ketoacidosis and almost half of the patients have type 1 diabetes-associated antibodies at presentation. Rapid loss of residual beta-cell function with a lack of honeymoon phase is typical. Certain human leukocyte antigen risk genes for prototypical type 1 diabetes that develops in children and young adults are also commonly found in patients with immune checkpoint inhibitor-induced type 1 diabetes. Summary: Immune checkpoint inhibitor-induced type 1 diabetes presenting with diabetic ketoacidosis is a life-threatening adverse event of cancer immunotherapy. Healthcare providers should be aware of this adverse event to prevent morbidity and mortality related to diabetic ketoacidosis. Developing guidelines to identify and monitor risk groups are of utmost importance.
MeSH term(s)	Adolescent ; Adult ; Antibodies, Monoclonal/adverse effects ; Antibodies, Monoclonal/therapeutic use ; Antineoplastic Agents, Immunological/adverse effects ; Cell Cycle Checkpoints/immunology ; Child ; Diabetes Mellitus, Type 1/etiology ; Diabetes Mellitus, Type 1/immunology ; Diabetic Ketoacidosis/etiology ; Diabetic Ketoacidosis/immunology ; Humans ; Immunotherapy/adverse effects ; Neoplasms/drug therapy ; Neoplasms/pathology ; Protein Kinase Inhibitors/adverse effects ; Protein Kinase Inhibitors/therapeutic use ; Young Adult
Chemical Substances	Antibodies, Monoclonal ; Antineoplastic Agents, Immunological ; Protein Kinase Inhibitors
Language	English
Publishing date	2020-07-03
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	2272017-0
ISSN	1752-2978 ; 1752-296X
ISSN (online)	1752-2978
ISSN	1752-296X
DOI	10.1097/MED.0000000000000546
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Article ; Online: Self-Antigens Targeted by Regulatory T Cells in Type 1 Diabetes

Angela M. Mitchell / Aaron W. Michels

International Journal of Molecular Sciences, Vol 23, Iss 3155, p

2022 Volume 3155

Abstract	While progress has been made toward understanding mechanisms that lead to the development of autoimmunity, there is less knowledge regarding protective mechanisms from developing such diseases. For example, in type 1 diabetes (T1D), the immune-mediated form of diabetes, the role of pathogenic T cells in the destruction of pancreatic islets is well characterized, but immune-mediated mechanisms that contribute to T1D protection have not been fully elucidated. One potential protective mechanism includes the suppression of immune responses by regulatory CD4 T cells (Tregs) that recognize self-peptides from islets presented by human leukocyte antigen (HLA) class II molecules. In this review, we summarize what is known about the antigenic self-peptides recognized by Tregs in the context of T1D.
Keywords	regulatory T cells ; type 1 diabetes ; islet autoimmunity ; antigen-specific therapy ; Biology (General) ; QH301-705.5 ; Chemistry ; QD1-999
Language	English
Publishing date	2022-03-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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