Affiliation:
1. *Program in Cellular and Molecular Medicine, Boston Children’s Hospital, Harvard Medical School, Boston, MA; and
2. †Harvard-MIT Health Sciences and Technology, Harvard Medical School, Boston, MA
Abstract
Abstract
Lupus susceptibility results from the combined effects of numerous genetic loci, but the contribution of these loci to disease pathogenesis has been difficult to study due to the large cellular heterogeneity of the autoimmune immune response. We performed single-cell RNA, BCR, and TCR sequencing of splenocytes from mice with multiple polymorphic lupus susceptibility loci. We not only observed lymphocyte and myeloid expansion, but we also characterized changes in subset frequencies and gene expression, such as decreased CD8 and marginal zone B cells and increased Fcrl5- and Cd5l-expressing macrophages. Clonotypic analyses revealed expansion of B and CD4 clones, and TCR repertoires from lupus-prone mice were distinguishable by algorithmic specificity prediction and unsupervised machine learning classification. Myeloid differential gene expression, metabolism, and altered ligand–receptor interaction were associated with decreased Ag presentation. This dataset provides novel mechanistic insight into the pathophysiology of a spontaneous model of lupus, highlighting potential therapeutic targets for autoantibody-mediated disease.
Funder
HHS | NIH | National Institute of Allergy and Infectious Diseases
HHS | NIH | National Institute of Arthritis and Musculoskeletal and Skin Diseases
HHS | NIH | National Institute of General Medical Sciences
Publisher
The American Association of Immunologists
Subject
Immunology,Immunology and Allergy
Cited by
5 articles.
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