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

ABSTRACT: 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 CD20loCD27hiCD38hiHLA-DRint plasmablasts, CD86+CD14loCD16+ non-classical monocytes and two subsets of CD56dimHLA-DR+IFN-?+ NK cells were increased in patients with HT. Subsets of CD56dimCD69+HLA-DR- NK cells and CD8+ TEMRA cells, both expressing IFN-?, 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.

SUBMITTER: Magnusson L

PROVIDER: S-EPMC7047233 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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

Magnusson Louise L Barcenilla Hugo H Pihl Mikael M Bensing Sophie S Espes Daniel D Carlsson Per-Ola PO Casas Rosaura R

Frontiers in immunology 20200221

Although there is evidence that autoimmune diseases share similar immunogenetic mechanisms, studies comparing peripheral CD45<sup>+</sup> 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 ...[more]

PMID: 32153591

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Project description:ObjectiveAccumulating evidence from microbial studies have highlighted the modulatory roles of intestinal microbes in numerous human diseases, however, the shared microbial signatures across different diseases remain relatively unclear.MethodsTo consolidate existing knowledge across multiple studies, we performed meta-analyses of 17 disease types, covering 34 case-control datasets of 16S rRNA sequencing data, to identify shared alterations among different diseases. Furthermore, the impact of a microbial species, Lactobacillus salivarius, was established in a dextran sodium sulphate-induced colitis model and a collagen type II-induced arthritis mouse model.ResultsMicrobial alterations among autoimmune diseases were substantially more consistent compared with that of other diseases (cancer, metabolic disease and nervous system disease), with microbial signatures exhibiting notable discriminative power for disease prediction. Autoimmune diseases were characterized by the enrichment of Enterococcus, Veillonella, Streptococcus and Lactobacillus and the depletion of Ruminococcus, Gemmiger, Oscillibacter, Faecalibacterium, Lachnospiracea incertae sedis, Anaerostipes, Coprococcus, Alistipes, Roseburia, Bilophila, Barnesiella, Dorea, Ruminococcus2, Butyricicoccus, Phascolarctobacterium, Parabacteroides and Odoribacter, among others. Functional investigation of L. salivarius, whose genus was commonly enriched in numerous autoimmune diseases, demonstrated protective roles in two separate inflammatory mouse models.ConclusionOur study highlights a strong link between autoimmune diseases and the gut microbiota, with notably consistent microbial alterations compared with that of other diseases, indicating that therapeutic strategies that target the gut microbiome may be transferable across different autoimmune diseases. Functional validation of L. salivarius highlighted that bacterial genera associated with disease may not always be antagonistic, but may represent protective or adaptive responses to disease.

Dataset Information

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

Publications

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

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