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Review
. 2021 Oct 1:12:751701.
doi: 10.3389/fimmu.2021.751701. eCollection 2021.

Insights From Single Cell RNA Sequencing Into the Immunology of Type 1 Diabetes- Cell Phenotypes and Antigen Specificity

Affiliations
Review

Insights From Single Cell RNA Sequencing Into the Immunology of Type 1 Diabetes- Cell Phenotypes and Antigen Specificity

Stephanie J Hanna et al. Front Immunol. .

Abstract

In the past few years, huge advances have been made in techniques to analyse cells at an individual level using RNA sequencing, and many of these have precipitated exciting discoveries in the immunology of type 1 diabetes (T1D). This review will cover the first papers to use scRNAseq to characterise human lymphocyte phenotypes in T1D in the peripheral blood, pancreatic lymph nodes and islets. These have revealed specific genes such as IL-32 that are differentially expressed in islet -specific T cells in T1D. scRNAseq has also revealed wider gene expression patterns that are involved in T1D and can predict its development even predating autoantibody production. Single cell sequencing of TCRs has revealed V genes and CDR3 motifs that are commonly used to target islet autoantigens, although truly public TCRs remain elusive. Little is known about BCR repertoires in T1D, but scRNAseq approaches have revealed that insulin binding BCRs commonly use specific J genes, share motifs between donors and frequently demonstrate poly-reactivity. This review will also summarise new developments in scRNAseq technology, the insights they have given into other diseases and how they could be leveraged to advance research in the type 1 diabetes field to identify novel biomarkers and targets for immunotherapy.

Keywords: BCR - B cell receptor; TCR - T cell receptor; immunology; lymphocytes; scRNAseq; type 1 diabetes.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

References

    1. Ahmed S, Cerosaletti K, James E, Long SA, Mannering S, Speake C, et al. . Standardizing T-Cell Biomarkers in Type 1 Diabetes: Challenges and Recent Advances. Diabetes (2019) 68:1366–79. doi: 10.2337/db19-0119 - DOI - PMC - PubMed
    1. Leete P, Oram RA, McDonald TJ, Shields BM, Ziller C, TIGI study team et al. . Studies of Insulin and Proinsulin in Pancreas and Serum Support the Existence of Aetiopathological Endotypes of Type 1 Diabetes Associated With Age at Diagnosis. Diabetologia (2020) 63:1258–67. doi: 10.1007/s00125-020-05115-6 - DOI - PMC - PubMed
    1. Hanna SJ, Powell WE, Long AE, Robinson EJS, Davies J, Megson C, et al. . Slow Progressors to Type 1 Diabetes Lose Islet Autoantibodies Over Time, Have Few Islet Antigen-Specific CD8+ T Cells and Exhibit a Distinct CD95hi B Cell Phenotype. Diabetologia (2020) 63:1174–85. doi: 10.1007/s00125-020-05114-7 - DOI - PMC - PubMed
    1. Powell WE, Hanna SJ, Hocter CN, Robinson E, Davies J, Dunseath GJ, et al. . Loss of CXCR3 Expression on Memory B Cells in Individuals With Long-Standing Type 1 Diabetes. Diabetologia (2018) 61:1794–803. doi: 10.1007/s00125-018-4651-x - DOI - PMC - PubMed
    1. Rahman AH, Homann D. Mass Cytometry and Type 1 Diabetes Research in the Age of Single-Cell Data Science. Curr Opin Endocrinol Diabetes Obes (2020) 27:231–9. doi: 10.1097/MED.0000000000000549 - DOI - PMC - PubMed

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