PT  - JOURNAL ARTICLE
AU  - Akama-Garren, Elliot H.
AU  - Carroll, Michael C.
TI  - Lupus Susceptibility Loci Predispose Mice to Clonal Lymphocytic Responses and Myeloid Expansion
AID  - 10.4049/jimmunol.2200098
DP  - 2022 May 15
TA  - The Journal of Immunology
PG  - 2403--2424
VI  - 208
IP  - 10
4099  - http://www.jimmunol.org/content/208/10/2403.short
4100  - http://www.jimmunol.org/content/208/10/2403.full
SO  - J. Immunol.2022 May 15; 208
AB  - Lupus susceptibility loci lead to emergence of novel myeloid subpopulations.Myeloid cells from lupus mice have decreased metabolism and Ag presentation.Algorithmic specificity prediction distinguishes TCRs from autoimmune mice.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.This article is featured in Top Reads, p.