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AKT Hyperphosphorylation and T Cell Exhaustion in Down Syndrome
Down syndrome (DS) is associated with increased susceptibility to infections, auto-immunity, immunodeficiency and haematological malignancies. The exact underlying immunological pathophysiology is still unclear. The immunophenotype and clinical characteristics of DS resemble those of Activated PI3K...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Frontiers Media S.A.
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8866941/ https://www.ncbi.nlm.nih.gov/pubmed/35222360 http://dx.doi.org/10.3389/fimmu.2022.724436 |
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author | Peeters, Daphne Pico-Knijnenburg, Ingrid Wieringa, Douwe Rad, Mandana Cuperus, Roos Ruige, Madelon Froeling, Frank Zijp, Gerda W. van der Burg, Mirjam Driessen, Gertjan J. A. |
author_facet | Peeters, Daphne Pico-Knijnenburg, Ingrid Wieringa, Douwe Rad, Mandana Cuperus, Roos Ruige, Madelon Froeling, Frank Zijp, Gerda W. van der Burg, Mirjam Driessen, Gertjan J. A. |
author_sort | Peeters, Daphne |
collection | PubMed |
description | Down syndrome (DS) is associated with increased susceptibility to infections, auto-immunity, immunodeficiency and haematological malignancies. The exact underlying immunological pathophysiology is still unclear. The immunophenotype and clinical characteristics of DS resemble those of Activated PI3K Delta Syndrome (APDS), in which the PI3K/AKT/mTOR pathway is overactivated. We hypothesized that T cell exhaustion and the hyperactivation of the AKT signalling pathway is also present in immune cells of children with DS. In this observational non-interventional cohort study we collected blood samples of children with DS (n=22) and healthy age-matched controls (n=21) for flowcytometric immunophenotyping, phospho-flow AKT analysis and exhaustion analysis of T cells. The median age was 5 years (range 1-12y). Total T and NK cells were similar for both groups, but absolute values and transitional B cells, naive memory B cells and naive CD4+ and CD8+ T cells were lower in DS. pAKT and AKT were increased for CD3+ and CD4+ T cells and CD20+ B cells in children with DS. Total AKT was also increased in CD8+ T cells. Children with DS showed increased expression of inhibitory markers Programmed cell dealth-1 (PD-1), CD244 and CD160 on CD8+ T cells and increased PD-1 and CD244+ expression on CD4+ T cells, suggesting T cell exhaustion. Children with DS show increased pAKT and AKT and increased T cell exhaustion, which might contribute to their increased susceptibility to infections, auto immunity and haematological malignancies. |
format | Online Article Text |
id | pubmed-8866941 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-88669412022-02-25 AKT Hyperphosphorylation and T Cell Exhaustion in Down Syndrome Peeters, Daphne Pico-Knijnenburg, Ingrid Wieringa, Douwe Rad, Mandana Cuperus, Roos Ruige, Madelon Froeling, Frank Zijp, Gerda W. van der Burg, Mirjam Driessen, Gertjan J. A. Front Immunol Immunology Down syndrome (DS) is associated with increased susceptibility to infections, auto-immunity, immunodeficiency and haematological malignancies. The exact underlying immunological pathophysiology is still unclear. The immunophenotype and clinical characteristics of DS resemble those of Activated PI3K Delta Syndrome (APDS), in which the PI3K/AKT/mTOR pathway is overactivated. We hypothesized that T cell exhaustion and the hyperactivation of the AKT signalling pathway is also present in immune cells of children with DS. In this observational non-interventional cohort study we collected blood samples of children with DS (n=22) and healthy age-matched controls (n=21) for flowcytometric immunophenotyping, phospho-flow AKT analysis and exhaustion analysis of T cells. The median age was 5 years (range 1-12y). Total T and NK cells were similar for both groups, but absolute values and transitional B cells, naive memory B cells and naive CD4+ and CD8+ T cells were lower in DS. pAKT and AKT were increased for CD3+ and CD4+ T cells and CD20+ B cells in children with DS. Total AKT was also increased in CD8+ T cells. Children with DS showed increased expression of inhibitory markers Programmed cell dealth-1 (PD-1), CD244 and CD160 on CD8+ T cells and increased PD-1 and CD244+ expression on CD4+ T cells, suggesting T cell exhaustion. Children with DS show increased pAKT and AKT and increased T cell exhaustion, which might contribute to their increased susceptibility to infections, auto immunity and haematological malignancies. Frontiers Media S.A. 2022-02-10 /pmc/articles/PMC8866941/ /pubmed/35222360 http://dx.doi.org/10.3389/fimmu.2022.724436 Text en Copyright © 2022 Peeters, Pico-Knijnenburg, Wieringa, Rad, Cuperus, Ruige, Froeling, Zijp, van der Burg and Driessen https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Immunology Peeters, Daphne Pico-Knijnenburg, Ingrid Wieringa, Douwe Rad, Mandana Cuperus, Roos Ruige, Madelon Froeling, Frank Zijp, Gerda W. van der Burg, Mirjam Driessen, Gertjan J. A. AKT Hyperphosphorylation and T Cell Exhaustion in Down Syndrome |
title | AKT Hyperphosphorylation and T Cell Exhaustion in Down Syndrome |
title_full | AKT Hyperphosphorylation and T Cell Exhaustion in Down Syndrome |
title_fullStr | AKT Hyperphosphorylation and T Cell Exhaustion in Down Syndrome |
title_full_unstemmed | AKT Hyperphosphorylation and T Cell Exhaustion in Down Syndrome |
title_short | AKT Hyperphosphorylation and T Cell Exhaustion in Down Syndrome |
title_sort | akt hyperphosphorylation and t cell exhaustion in down syndrome |
topic | Immunology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8866941/ https://www.ncbi.nlm.nih.gov/pubmed/35222360 http://dx.doi.org/10.3389/fimmu.2022.724436 |
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