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| Status |
Public on Mar 14, 2022 |
| Title |
Lupus susceptibility loci predispose mice to clonal lymphocytic responses and myeloid expansion |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
Other
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| Summary |
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, B cell receptor (BCR), and T cell receptor (TCR) sequencing of splenocytes from mice with multiple polymorphic lupus susceptibility loci. We not only observed lymphocyte and myeloid expansion, but 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 antigen presentation. This dataset provides novel mechanistic insight into the pathophysiology of a spontaneous model of lupus, highlighting potential therapeutic targets for autoantibody mediated disease.
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| Overall design |
scRNA-seq, scBCR-seq, and scTCR-seq was performed on 4 mice (2 controls and 2 autoimmune mice)
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| Contributor(s) |
Carroll MC, Akama-Garren EH |
| Citation(s) |
35477687 |
| NIH grant(s) |
| Grant ID |
Grant title |
Affiliation |
Name |
| F30 AI160909 |
Follicular helper T cells as drivers of epitope spreading |
HARVARD UNIVERSITY (MEDICAL SCHOOL) |
Elliot Hideki Akama-Garren |
| R01 AR074105 |
Evolution of autoreactive GC and epitope spreading in lupus |
CHILDREN'S HOSPITAL |
Michael Craig Carroll |
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| |
| Submission date |
Dec 29, 2021 |
| Last update date |
May 04, 2022 |
| Contact name |
Elliot Akama-Garren |
| Organization name |
Harvard Medical School
|
| Street address |
200 Longwood Ave
|
| City |
Boston |
| State/province |
MA |
| ZIP/Postal code |
02115 |
| Country |
USA |
| |
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| Platforms (1) |
| GPL24247 |
Illumina NovaSeq 6000 (Mus musculus) |
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| Samples (12)
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| Relations |
| BioProject |
PRJNA793042 |
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