The Expanding Role of Natural Killer Cells in Type 1 Diabetes and Immunotherapy

Fraker, Christopher A.; Bayer, Allison L.

doi:10.1007/s11892-016-0806-7

Cited by 26 publications

(28 citation statements)

References 114 publications

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“…Most studies addressing NK cells in T1D have focused on their cytotoxic function, whereas studies investigating the phenotype of cell subsets are limited (52,53). It has been recently shown that children with newly diagnosed T1D had reduced frequencies of CD16 + CD56 dim and CD16 − CD56 dim NK cell subsets than HC (32).…”

Section: Discussionmentioning

confidence: 99%

Mass Cytometry Studies of Patients With Autoimmune Endocrine Diseases Reveal Distinct Disease-Specific Alterations in Immune Cell Subsets

et al. 2020

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Although there is evidence that autoimmune diseases share similar immunogenetic mechanisms, studies comparing peripheral CD45 + cells from patients with autoimmune endocrine diseases in parallel are limited. In this study, we applied high-dimensional single-cell mass cytometry to phenotypically characterize PBMC from patients with new-onset (N-T1D) and long-standing type 1 diabetes, Hashimoto's thyroiditis (HT), Graves' disease and autoimmune Addison's disease (AD), as well as healthy controls. The frequency of CD20 lo CD27 hi CD38 hi HLA-DR int plasmablasts, CD86 + CD14 lo CD16 + non-classical monocytes and two subsets of CD56 dim HLA-DR + IFN-γ + NK cells were increased in patients with HT. Subsets of CD56 dim CD69 + HLA-DR − NK cells and CD8 + TEMRA cells, both expressing IFN-γ, were expanded and reduced, respectively, in the N-T1D group. In addition, patients with AD were characterized by an increased percentage of central memory CD8 + T cells that expressed CCR4, GATA3, and IL-2. We demonstrate that patients with N-T1D, HT, and AD had altered frequencies of distinct subsets within antigen-presenting and cytotoxic cell lineages. Previously unreported alterations of specific cell subsets were identified in samples from patients with HT and AD. Our study might contribute to a better understanding of shared and diverging immunological features between autoimmune endocrine diseases.

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Section: Discussionmentioning

confidence: 99%

Mass Cytometry Studies of Patients With Autoimmune Endocrine Diseases Reveal Distinct Disease-Specific Alterations in Immune Cell Subsets

et al. 2020

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“…However, the exact role of this latter subset in normal physiological conditions, as well as in autoimmune diseases, remains to be defined. enterovirus) [16]. 2f-h and Supporting information, Fig.…”

Section: Discussionmentioning

confidence: 99%

“…The current literature deals mainly with two main subsets of NK cells: (1) CD56 dim CD16 + are mature cells forming the majority of NK cells in peripheral blood; and (2) CD56 bright CD16cells are considered to be immature NK cells [15]. These cells have also been termed NK eff cells and NK reg cells, respectively [16]. There is also an intermediate subset characterized as CD56 bright CD16 + [15], and some studies suggest a fourth population of NK cells, which express CD56 but lack CD16 (CD56 dim CD16 -) [17].…”

Section: Discussionmentioning

confidence: 99%

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A study of 51 subtypes of peripheral blood immune cells in newly diagnosed young type 1 diabetes patients

Oras

Peet

Giese

et al. 2019

Clinical and Experimental Immunology

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Type 1 diabetes (T1D) results from autoimmune destruction of insulinproducing beta cells in pancreatic islets. Various immune cell populations are involved in disease development and natural course. However, to our knowledge, so far there are no comprehensive comparative investigations of all main immune cell populations and their most important subsets at the onset of disease. Therefore, in the current study, we analyzed 51 peripheral blood immune cell populations in 22 young T1D patients and in 25 age-matched controls using a comprehensive polychromatic flow cytometry panel developed for whole blood by the COST Action no. BM0907 ENTIRE (European Network for Translational Immunology Research and Education: From Immunomonitoring to Personalized Immunotherapy) consortium. We found that in T1D patients, frequencies and absolute counts of natural killer (NK) cells, dendritic cells (DC) and T cells, aswell as their respective subsets, were significantly altered compared to controls. Further, we observed that changes in several cell populations (e.g. CD14 + CD16 + non-classical monocytes, plasmablasts) were dependent on the age of the patient. In addition to age-related changes, we also found that alterations in immune cell patterns were associated with parameters such as the presence of ketoacidosis and C-peptide serum levels. Our study provides a foundation for future studies investigating different cell lineages and their role in T1D and illustrates the value of polychromatic flow cytometry for evaluating all main peripheral immune cells and their subsets in whole blood samples.

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“…Possible roles for innate immune cells exist not only in the initiation stage of autoimmune diseases but also in the modulation and propagation of inflammation and tissue destruction. Such roles have been proposed for neutrophils (4), natural killer cells (5, 6), macrophages (7), dendritic cells (8, 9), innate lymphoid cells (10), and mast cells (11). Eosinophils have been recognized as a part of the inflammatory infiltrate in several organ-specific autoimmune diseases, but their potential role in autoimmune diseases has not been addressed comprehensively.…”

Section: Introductionmentioning

confidence: 99%

Eosinophils in Autoimmune Diseases

2017

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Eosinophils are multifunctional granulocytes that contribute to initiation and modulation of inflammation. Their role in asthma and parasitic infections has long been recognized. Growing evidence now reveals a role for eosinophils in autoimmune diseases. In this review, we summarize the function of eosinophils in inflammatory bowel diseases, neuromyelitis optica, bullous pemphigoid, autoimmune myocarditis, primary biliary cirrhosis, eosinophilic granulomatosis with polyangiitis, and other autoimmune diseases. Clinical studies, eosinophil-targeted therapies, and experimental models have contributed to our understanding of the regulation and function of eosinophils in these diseases. By examining the role of eosinophils in autoimmune diseases of different organs, we can identify common pathogenic mechanisms. These include degranulation of cytotoxic granule proteins, induction of antibody-dependent cell-mediated cytotoxicity, release of proteases degrading extracellular matrix, immune modulation through cytokines, antigen presentation, and prothrombotic functions. The association of eosinophilic diseases with autoimmune diseases is also examined, showing a possible increase in autoimmune diseases in patients with eosinophilic esophagitis, hypereosinophilic syndrome, and non-allergic asthma. Finally, we summarize key future research needs.

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The Expanding Role of Natural Killer Cells in Type 1 Diabetes and Immunotherapy

Cited by 26 publications

References 114 publications

Mass Cytometry Studies of Patients With Autoimmune Endocrine Diseases Reveal Distinct Disease-Specific Alterations in Immune Cell Subsets

Mass Cytometry Studies of Patients With Autoimmune Endocrine Diseases Reveal Distinct Disease-Specific Alterations in Immune Cell Subsets

A study of 51 subtypes of peripheral blood immune cells in newly diagnosed young type 1 diabetes patients

Eosinophils in Autoimmune Diseases

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