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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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    1. Mateusz Legut & Zoran Gajic & Maria Guarino & Zharko Daniloski & Jahan A. Rahman & Xinhe Xue & Congyi Lu & Lu Lu & Eleni P. Mimitou & Stephanie Hao & Teresa Davoli & Catherine Diefenbach & Peter Smibe, 2022. "A genome-scale screen for synthetic drivers of T cell proliferation," Nature, Nature, vol. 603(7902), pages 728-735, March.
    2. Peter A. Szabo & Hanna Mendes Levitin & Michelle Miron & Mark E. Snyder & Takashi Senda & Jinzhou Yuan & Yim Ling Cheng & Erin C. Bush & Pranay Dogra & Puspa Thapa & Donna L. Farber & Peter A. Sims, 2019. "Single-cell transcriptomics of human T cells reveals tissue and activation signatures in health and disease," Nature Communications, Nature, vol. 10(1), pages 1-16, December.
    3. Aparna Nathan & Samira Asgari & Kazuyoshi Ishigaki & Cristian Valencia & Tiffany Amariuta & Yang Luo & Jessica I. Beynor & Yuriy Baglaenko & Sara Suliman & Alkes L. Price & Leonid Lecca & Megan B. Mur, 2022. "Single-cell eQTL models reveal dynamic T cell state dependence of disease loci," Nature, Nature, vol. 606(7912), pages 120-128, June.
    4. Hironori Ueda & Joanna M. M. Howson & Laura Esposito & Joanne Heward & Snook & Giselle Chamberlain & Daniel B. Rainbow & Kara M. D. Hunter & Annabel N. Smith & Gianfranco Di Genova & Mathias H. Herr &, 2003. "Association of the T-cell regulatory gene CTLA4 with susceptibility to autoimmune disease," Nature, Nature, vol. 423(6939), pages 506-511, May.
    5. Emily S. Wong & Bianca M. Schmitt & Anastasiya Kazachenka & David Thybert & Aisling Redmond & Frances Connor & Tim F. Rayner & Christine Feig & Anne C. Ferguson-Smith & John C. Marioni & Duncan T. Odo, 2017. "Interplay of cis and trans mechanisms driving transcription factor binding and gene expression evolution," Nature Communications, Nature, vol. 8(1), pages 1-13, December.
    6. Yukinori Okada & Di Wu & Gosia Trynka & Towfique Raj & Chikashi Terao & Katsunori Ikari & Yuta Kochi & Koichiro Ohmura & Akari Suzuki & Shinji Yoshida & Robert R. Graham & Arun Manoharan & Ward Ortman, 2014. "Genetics of rheumatoid arthritis contributes to biology and drug discovery," Nature, Nature, vol. 506(7488), pages 376-381, February.
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