University of Oulu

Gazali, A.M., Schroderus, A., Näntö-Salonen, K. et al. Mucosal-associated invariant T cell alterations during the development of human type 1 diabetes. Diabetologia 63, 2396–2409 (2020). https://doi.org/10.1007/s00125-020-05257-7

Mucosal-associated invariant T cell alterations during the development of human type 1 diabetes

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Author: Gazali, Ahmad M.1; Schroderus, Anna-Mari1; Näntö-Salonen, Kirsti2;
Organizations: 1Department of Clinical Microbiology, Institute of Clinical Medicine, University of Eastern Finland, Kuopio, Finland
2Department of Pediatrics, Turku University Hospital, Turku, Finland
3Department of Medicine, Kuopio University Hospital, Kuopio, Finland
4Institute of Public Health and Clinical Nutrition, University of Eastern Finland, Kuopio, Finland
5Clinical Nutrition and Obesity Center, Kuopio University Hospital, Kuopio, Finland
6Tampere Center for Child Health Research, Tampere University Hospital, Tampere, Finland
7Children’s Hospital, University of Helsinki and Helsinki University Hospital, Helsinki, Finland
8Research Program for Clinical and Molecular Metabolism, Faculty of Medicine, University of Helsinki, Helsinki, Finland
9Folkhälsan Research Center, Helsinki, Finland
10PEDEGO Research Unit, Department of Pediatrics, Medical Research Center, Oulu University Hospital and University of Oulu, Oulu, Finland
11Institute of Biomedicine, Research Centre for Integrative Physiology and Pharmacology, University of Turku, Turku, Finland
12Immunogenetics Laboratory, Institute of Biomedicine, University of Turku, Turku, Finland
13Clinical Microbiology, Turku University Hospital, Turku, Finland
14Eastern Finland Laboratory Centre (ISLAB), Kuopio, Finland
Format: article
Version: published version
Access: open
Online Access: PDF Full Text (PDF, 3.2 MB)
Persistent link: http://urn.fi/urn:nbn:fi-fe2020110288928
Language: English
Published: Springer Nature, 2020
Publish Date: 2020-11-02
Description:

Abstract

Aims/hypothesis: Mucosal-associated invariant T (MAIT) cells are innate-like T cells that recognise derivatives of bacterial riboflavin metabolites presented by MHC-Ib-related protein 1 (MR1) molecules and are important effector cells for mucosal immunity. Their development can be influenced by the intestinal microbiome. Since the development of type 1 diabetes has been associated with changes in the gut microbiome, this can be hypothesised to lead to alterations in circulating MAIT cells. Accordingly, peripheral blood MAIT cell alterations have been reported previously in patients with type 1 diabetes. However, a comprehensive analysis of the frequency and phenotype of circulating MAIT cells at different stages of type 1 diabetes progression is currently lacking.

Methods: We analysed the frequency, phenotype and functionality of peripheral blood MAIT cells, as well as γδ T cells, invariant natural killer T (iNKT) cells and natural killer (NK) cells with flow cytometry in a cross-sectional paediatric cohort (aged 2–15) consisting of 51 children with newly diagnosed type 1 diabetes, 27 autoantibody-positive (AAb+) at-risk children, and 113 healthy control children of similar age and HLA class II background. The frequency of MAIT cells was also assessed in a separate cross-sectional adult cohort (aged 19–39) of 33 adults with established type 1 diabetes and 37 healthy individuals of similar age.

Results: Children with newly diagnosed type 1 diabetes displayed a proportional increase of CD8⁻CD27⁻ MAIT cells compared with healthy control children (median 4.6% vs 3.1% of MAIT cells, respectively, p = 0.004), which was associated with reduced expression of C-C chemokine receptor (CCR)5 (median 90.0% vs 94.3% of MAIT cells, p = 0.02) and β7 integrin (median 73.5% vs 81.7% of MAIT cells, p = 0.004), as well as decreased production of IFN-γ (median 57.1% vs 69.3% of MAIT cells, p = 0.04) by the MAIT cells. The frequency of MAIT cells was also decreased in AAb⁺ children who later progressed to type 1 diabetes compared with healthy control children (median 0.44% vs 0.96% of CD3⁺ T cells, p = 0.04), as well as in adult patients with a short duration of type 1 diabetes (less than 6 years after diagnosis) compared with control individuals (median 0.87% vs 2.19% of CD3⁺ T cells, p = 0.007). No alterations in γδ T cell, iNKT cell or NK cell frequencies were observed in children with type 1 diabetes or in AAb⁺ children, with the exception of an increased frequency of IL-17A⁺ γδ T cells in children with newly diagnosed diabetes compared with healthy control children (median 1.58% vs 1.09% of γδ T cells, p = 0.002).

Conclusions/interpretation: Changes in the frequency and phenotype of circulating MAIT cells were detectable before, at the onset and after diagnosis of type 1 diabetes in cross-sectional cohorts. Our results suggest a possible temporal association between peripheral blood MAIT cell alterations and the clinical onset of type 1 diabetes.

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Series: Diabetologia
ISSN: 0012-186X
ISSN-E: 1432-0428
ISSN-L: 0012-186X
Volume: 63
Issue: 11
Pages: 2396 - 2409
DOI: 10.1007/s00125-020-05257-7
OADOI: https://oadoi.org/10.1007/s00125-020-05257-7
Type of Publication: A1 Journal article – refereed
Field of Science: 3121 General medicine, internal medicine and other clinical medicine
Subjects:
Funding: Open access funding provided by University of Eastern Finland (UEF) including Kuopio University Hospital. The study was supported by the Academy of Finland (Decision number 307320), the Sigrid Jusélius Foundation and the Finnish Diabetes Research Foundation. The DIPP study was supported by the Academy of Finland (Decision numbers 250114 and 286765), the Sigrid Jusélius Foundation and JDRF (grants 1-SRA-2016-342-M-R, 1-SRA-2019-732-M).
Copyright information: © The Author(s) 2020. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.
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