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The genetic basis of autoimmunity seen through the lens of T cell functional traits

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  • Kaitlyn A. Lagattuta

    (Harvard Medical School
    Brigham and Women’s Hospital and Harvard Medical School
    Brigham and Women’s Hospital and Harvard Medical School
    Broad Institute of MIT and Harvard)

  • Hannah L. Park

    (Harvard Medical School
    Brigham and Women’s Hospital and Harvard Medical School
    Brigham and Women’s Hospital and Harvard Medical School
    Broad Institute of MIT and Harvard)

  • Laurie Rumker

    (Harvard Medical School
    Brigham and Women’s Hospital and Harvard Medical School
    Brigham and Women’s Hospital and Harvard Medical School
    Broad Institute of MIT and Harvard)

  • Kazuyoshi Ishigaki

    (Harvard Medical School
    Brigham and Women’s Hospital and Harvard Medical School
    Brigham and Women’s Hospital and Harvard Medical School
    Broad Institute of MIT and Harvard)

  • Aparna Nathan

    (Harvard Medical School
    Brigham and Women’s Hospital and Harvard Medical School
    Brigham and Women’s Hospital and Harvard Medical School
    Broad Institute of MIT and Harvard)

  • Soumya Raychaudhuri

    (Harvard Medical School
    Brigham and Women’s Hospital and Harvard Medical School
    Brigham and Women’s Hospital and Harvard Medical School
    Broad Institute of MIT and Harvard)

Abstract

Autoimmune disease heritability is enriched in T cell-specific regulatory regions of the genome. Modern-day T cell datasets now enable association studies between single nucleotide polymorphisms (SNPs) and a myriad of molecular phenotypes, including chromatin accessibility, gene expression, transcriptional programs, T cell antigen receptor (TCR) amino acid usage, and cell state abundances. Such studies have identified hundreds of quantitative trait loci (QTLs) in T cells that colocalize with genetic risk for autoimmune disease. The key challenge facing immunologists today lies in synthesizing these results toward a unified understanding of the autoimmune T cell: which genes, cell states, and antigens drive tissue destruction?

Suggested Citation

  • Kaitlyn A. Lagattuta & Hannah L. Park & Laurie Rumker & Kazuyoshi Ishigaki & Aparna Nathan & Soumya Raychaudhuri, 2024. "The genetic basis of autoimmunity seen through the lens of T cell functional traits," Nature Communications, Nature, vol. 15(1), pages 1-6, December.
    • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-45170-w
    DOI: 10.1038/s41467-024-45170-w
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