Abstract
Objective: In systemic lupus erythematosus (SLE), widespread T cell infiltration into target organs contributes to inflammation and organ damage. Autoreactive T cells become aberrantly activated in this disease due to dysfunctional T cell receptor signaling that lowers the activation threshold. Characterizing the T cell repertoire can provide further insight into the specific homing and proliferation of these T cells into lupus target organs. In the spontaneous lupus model, MRL/lpr, the TCR repertoire has not been fully elucidated, especially for T cells infiltrating the brain. Our aim was to investigate and compare the TCR repertoire between MRL/lpr mice and its congenic controls, MRL/MpJ, and within MRL/lpr tissues. Methods: Spleen, salivary gland, and brain choroid plexus were isolated from female MRL/lpr mice and MRL/MpJ mice. The TCRβ CDR3 region was analyzed by multiplex PCRs and sequencing. Results: Significant differences were seen not only between the MRL/lpr and MRL/MpJ spleens, but also between MRL/lpr tissues. The TCR repertoire in MRL/lpr choroid plexus tissues had significantly increased clonality and sequence homology compared to MRL/lpr spleen and salivary gland. The consensus sequence, CASSQDWGGYEQYFF, was identified in the MRL/lpr choroid plexus repertoire. Conclusions: The TCR repertoire in lupus prone mice is not uniform between target organs, and suggests that T cells are specifically recruited into the choroid plexus of MRL/lpr mice. Further studies are needed to determine the antigen specificities for these infiltrating T cells in target organs of lupus mice, and their possible contribution to the pathogenesis of neuropsychiatric disease and other lupus manifestations.
Original language | English |
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Article number | 1476 |
Journal | Frontiers in Immunology |
Volume | 11 |
DOIs | |
State | Published - 17 Jul 2020 |
Bibliographical note
Publisher Copyright:© Copyright © 2020 Moore, Huang, Jain, Chalmers, Macian and Putterman.
Funding
Funding. EM was supported by the Gina M. Finzi Memorial Student Summer Fellowship Program and the Medical Scientist Training Program T32-GM007288. MH was supported by the Training Program in Cellular & Molecular Biology & Genetics T32-GM007491 from the National Institutes of Health, and CP by an R01 grant, AR065594, from the National Institute of Arthritis and Musculoskeletal Diseases.
Funders | Funder number |
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Medical Scientist Training Program | T32-GM007491, T32-GM007288 |
National Institutes of Health | |
National Institute of Arthritis and Musculoskeletal and Skin Diseases | R01AR065594 |
Keywords
- MRL/lpr
- T cell receptor
- choroid plexus
- neuropsychiatric lupus
- salivary gland
- systemic lupus erythematosus