Activation of GABA(A) receptors inhibits T cell proliferation

The major sites for fast synaptic inhibition in the central nervous system (CNS) are ion channels activated by γ-aminobutyric acid (GABA). These receptors are referred as GABA(A) receptors (GABA(A)R). Recent evidence indicates a role of GABA(A)R in modulating the immune response. This work aimed to...

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Bibliographic Details
Published in:PloS one 2021-05, Vol.16 (5), p.e0251632-e0251632
Main Authors: Sparrow, Emma L, James, Sonya, Hussain, Khiyam, Beers, Stephen A, Cragg, Mark S, Bogdanov, Yury D
Format: Article
Language:English
Subjects:
Animal welfare
Animals
Antibodies
Asthma
Benzodiazepines
Benzodiazepines - pharmacology
Biology and Life Sciences
Biotechnology industry
Cancer
Cancer vaccines
CD4-Positive T-Lymphocytes - metabolism
CD8-Positive T-Lymphocytes - metabolism
Cell activation
Cell growth
Cell proliferation
Cell Proliferation - drug effects
Central nervous system
Control
Cytokines
Dendritic cells
Editing
Ethics
GABA
Growth
Humans
Immune system
Immunology
Inflammation
Ion channels
Leukocyte migration
Lymphocytes
Lymphocytes T
Macrophages
Medical research
Medicine
Medicine and Health Sciences
Mice
Modulation
Pregnanolone - pharmacology
Receptors
Receptors, GABA - metabolism
Receptors, GABA-A - metabolism
Research and Analysis Methods
Signaling
T cells
Vaccines
γ-Aminobutyric acid
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Summary:The major sites for fast synaptic inhibition in the central nervous system (CNS) are ion channels activated by γ-aminobutyric acid (GABA). These receptors are referred as GABA(A) receptors (GABA(A)R). Recent evidence indicates a role of GABA(A)R in modulating the immune response. This work aimed to discern the role of GABA and GABA(A)Rs in human and mouse T cell activity. Mouse splenocytes or human peripheral blood mononuclear cells (PBMCs) were activated with anti-CD3 antibodies and the proliferation of both CD8+ and CD4+ T cells assessed through flow cytometry. Subsequently, the effects on T cell proliferation of either GABA(A)R modulation by diazepam that is also capable of activating mitochondrial based translocator protein (TSPO), alprazolam and allopregnanolone or inhibition by bicucculine methiodide (BMI) and (1,2,5,6-Tetrahydropyridin-4-yl)methylphosphinic acid (TPMPA) were assessed. Positive modulation of GABA(A)Rs either by benzodiazepines or the neurosteroid allopregnanolone inhibits both mouse and human T cell proliferation. GABAergic inhibition of T cell proliferation by benzodiazepines could be rescued by GABA(A)R blocking. Our data suggest that benzodiazepines influence T cell proliferation through both TSPO and GABA(A)Rs activation. We conclude that activation of GABA(A)Rs provides immunosuppression by inhibiting T cell proliferation.
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0251632