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

Kaitlyn A Lagattuta; Hannah L Park; Laurie Rumker; Kazuyoshi Ishigaki; Aparna Nathan; Soumya Raychaudhuri

doi:10.1038/s41467-024-45170-w

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

Nat Commun. 2024 Feb 8;15(1):1204. doi: 10.1038/s41467-024-45170-w.

Authors

Kaitlyn A Lagattuta^{1

2

3

4

5}, Hannah L Park^{1

2

3

4

5}, Laurie Rumker^{1

2

3

4

5}, Kazuyoshi Ishigaki^{1

2

3

4

6}, Aparna Nathan^#^{7

8

9

10

11}, Soumya Raychaudhuri^#^{12

13

14

15

16}

Affiliations

¹ Center for Data Sciences, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
² Division of Genetics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
³ Division of Rheumatology, Inflammation, and Immunity, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
⁴ Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
⁵ Department of Biomedical Informatics, Harvard Medical School, Boston, MA, USA.
⁶ Laboratory for Human Immunogenetics, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan.
⁷ Center for Data Sciences, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA. aparna_nathan@hms.harvard.edu.
⁸ Division of Genetics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA. aparna_nathan@hms.harvard.edu.
⁹ Division of Rheumatology, Inflammation, and Immunity, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA. aparna_nathan@hms.harvard.edu.
¹⁰ Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA, USA. aparna_nathan@hms.harvard.edu.
¹¹ Department of Biomedical Informatics, Harvard Medical School, Boston, MA, USA. aparna_nathan@hms.harvard.edu.
¹² Center for Data Sciences, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA. soumya@broadinstitute.org.
¹³ Division of Genetics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA. soumya@broadinstitute.org.
¹⁴ Division of Rheumatology, Inflammation, and Immunity, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA. soumya@broadinstitute.org.
¹⁵ Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA, USA. soumya@broadinstitute.org.
¹⁶ Department of Biomedical Informatics, Harvard Medical School, Boston, MA, USA. soumya@broadinstitute.org.

^# Contributed equally.

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?

Publication types

Review

MeSH terms

Autoimmune Diseases* / genetics
Autoimmunity / genetics
Genome-Wide Association Study
Humans
Phenotype
Polymorphism, Single Nucleotide
Quantitative Trait Loci / genetics
Receptors, Antigen, T-Cell / genetics
T-Lymphocytes*

Substances

Receptors, Antigen, T-Cell

Abstract

Publication types

MeSH terms

Substances

Grants and funding