Dataset Information

Fewer LAG-3⁺ T Cells in Relapsing-Remitting Multiple Sclerosis and Type 1 Diabetes.

ABSTRACT: The coinhibitory receptor lymphocyte activation gene 3 (LAG-3) is an immune checkpoint molecule that negatively regulates T cell activation, proliferation, and homeostasis. Blockade or deletion of LAG-3 in autoimmune-prone backgrounds or induced-disease models has been shown to exacerbate disease. We observed significantly fewer LAG-3⁺ CD4 and CD8 T cells from subjects with relapsing-remitting multiple sclerosis (RRMS) and type 1 diabetes. Low LAG-3 protein expression was linked to alterations in mRNA expression and not cell surface cleavage. Functional studies inhibiting LAG-3 suggest that in subjects with RRMS, LAG-3 retains its ability to suppress T cell proliferation. However, LAG-3 expression was associated with the expression of markers of apoptosis, indicating a role for low LAG-3 in T cell resistance to cell death. In T cells from subjects with RRMS, we observed a global dysregulation of LAG-3 expression stemming from decreased transcription and persisting after T cell stimulation. These findings further support the potential clinical benefits of a LAG-3 agonist in the treatment of human autoimmunity.

SUBMITTER: Jones BE

PROVIDER: S-EPMC8820445 | biostudies-literature | 2022 Feb

REPOSITORIES: biostudies-literature

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Fewer LAG-3<sup>+</sup> T Cells in Relapsing-Remitting Multiple Sclerosis and Type 1 Diabetes.

Jones Britta E BE Maerz Megan D MD Bahnson Henry T HT Somasundaram Ashwin A McCarthy Lucas H LH Speake Cate C Buckner Jane H JH

Journal of immunology (Baltimore, Md. : 1950) 20220112 3

The coinhibitory receptor lymphocyte activation gene 3 (LAG-3) is an immune checkpoint molecule that negatively regulates T cell activation, proliferation, and homeostasis. Blockade or deletion of LAG-3 in autoimmune-prone backgrounds or induced-disease models has been shown to exacerbate disease. We observed significantly fewer LAG-3<sup>+</sup> CD4 and CD8 T cells from subjects with relapsing-remitting multiple sclerosis (RRMS) and type 1 diabetes. Low LAG-3 protein expression was linked to al ...[more]

PMID: 35022272

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Project description:BackgroundCortical, thalamic and hippocampal gray matter atrophy in relapsing-remitting MS (RRMS) is associated cognitive deficits. However, the role of interconnecting white matter pathways including the fornix, cingulum, and uncinate fasciculus (UF) is less well studied.ObjectiveTo assess MS damage to a hippocampal-thalamic-prefrontal network and the relative contributions of its components to specific cognitive domains.MethodsWe calculated diffusion tensor fractional anisotropy (FA) in the fornix, cingulum and UF as well as thalamic and hippocampal volumes in 27 RRMS patients and 20 healthy controls. A neuropsychological battery was administered and 4 core tests known to be sensitive to MS changes were used to assess cognitive impairment. To determine the relationships between structure and cognition, all tests were grouped into 4 domains: attention/executive function, processing speed, verbal memory, and spatial memory. Univariate correlations with structural measures and depressive symptoms identified potential contributors to cognitive performance and subsequent linear regression determined their relative effects on performance in each domain. For significant predictors, we also explored the effects of laterality and axial versus radial diffusivity.ResultsRRMS patients had worse performance on the Symbol Digit Modalities Test, but no significant impairment in the 4 cognitive domains. RRMS had reduced mean FA of all 3 pathways and reduced thalamic and hippocampal volumes compared to controls. In RRMS we found that thalamic volume and BDI predicted attention/executive function, UF FA predicted processing speed, thalamic volume predicted verbal memory, and UF FA and BDI predicted spatial memory.ConclusionsHippocampal-thalamic-prefrontal disruption affects cognitive performance in early RRMS with mild to minimal cognitive impairment, confirming both white and gray matter involvement in MS and demonstrating utility in assessing functional networks to monitor cognition.

Dataset Information

Fewer LAG-3⁺ T Cells in Relapsing-Remitting Multiple Sclerosis and Type 1 Diabetes.

Publications

Fewer LAG-3<sup>+</sup> T Cells in Relapsing-Remitting Multiple Sclerosis and Type 1 Diabetes.

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Dataset Information

Fewer LAG-3+ T Cells in Relapsing-Remitting Multiple Sclerosis and Type 1 Diabetes.

Publications

Fewer LAG-3<sup>+</sup> T Cells in Relapsing-Remitting Multiple Sclerosis and Type 1 Diabetes.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

Fewer LAG-3⁺ T Cells in Relapsing-Remitting Multiple Sclerosis and Type 1 Diabetes.