Immune tolerance fails in autoimmune polyendocrine syndrome type 1 (APS-1) because of mutations. We have used single cell transcriptomics to characterize regulatory T cells (Tregs) sorted directly from blood and from expanded Tregs in APS-1 patients compared to healthy controls. We revealed only CD52 and LTB (down) and TXNIP (up) as consistently differentially expressed genes in the datasets. There were furthermore no large differences of the TCR-repertoire of expanded Tregs between the cohorts, but unique patients showed a more restricted use of specific clonotypes. We also found that expanded Tregs from APS-1 patients had similar suppressive capacity as controls in co-culture assays, despite expanding faster and having more exhausted cells. Our results suggest that APS-1 patients do not have intrinsic defects in their Treg functionality, and that their Tregs can be expanded for potential therapeutic applications.
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http://dx.doi.org/10.1016/j.isci.2024.109610 | DOI Listing |
Ann Nutr Metab
January 2025
Department of Translational Medical Science, University of Naples Federico II, Napoli, Italy.
Background: Knowledge of the complex interplay between gut microbiota and human health is gradually increasing as it has just recently been a field of such great interest.
Summary: Recent studies have reported that communities of microorganisms inhabiting the gut influence the immune system through cellular responses and shape many physiological and pathophysiological aspects of the body, including muscle and bone metabolism (formation and resorption). Specifically, the gut microbiota affects skeletal homeostasis through changes in host metabolism, the immune system, hormone secretion, and the gut-brain axis.
Kidney Int
January 2025
Centre for Inflammatory Diseases, Department of Medicine, School of Clinical Sciences, Monash University, Clayton, Australia. Electronic address:
Anti-glomerular basement membrane (anti-GBM) disease is accompanied by insufficient antigen-specific T regulatory cells (Tregs) and clonally expanded antigen-specific T conventional cells (Tconvs). In particular, this applied to the immunodominant T cell auto- epitope of type IV collagen, α3(IV)NC1135-145 , presented by HLA-DR15. Here, we investigated whether Tregs engineered to express GBM-T cell receptors (TCR) specific for α3(IV)NC1135- 145 better suppress autoimmunity.
View Article and Find Full Text PDFCommun Biol
January 2025
San Raffaele Diabetes Research Institute, IRCCS Ospedale San Raffaele Milan, Milan, Italy.
Tregs for adoptive therapy are traditionally expanded ex vivo using high doses of IL-2. However, the final Treg product has limited survival once infused in patients, potentially affecting therapeutic effectiveness. Here, we tested a novel expansion protocol in which highly purified naïve Tregs were expanded with a combination of IL-7 and IL-15, in the absence of IL-2.
View Article and Find Full Text PDFRegulatory T cells (Tregs) are increasingly being recognized for their role in promoting tissue repair. In this issue of the JCI, Chen et al. found that Tregs at the site of bone injury contribute to bone repair.
View Article and Find Full Text PDFGastro Hep Adv
September 2024
Department of Immunology, Leiden University Medical Center, Leiden, the Netherlands.
Background And Aims: Refractory celiac disease type II (RCDII) is characterized by a clonally expanded aberrant cell population in the small intestine. The role of other tissue-resident immune subsets in RCDII is unknown. Here, we characterized CD8 and CD4 T cells in RCDII duodenum at the single-cell level and .
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