Activation of GABA(A) receptors inhibits T cell proliferation.

<h4>Background</h4>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 immun...

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Autores principales:	Emma L Sparrow, Sonya James, Khiyam Hussain, Stephen A Beers, Mark S Cragg, Yury D Bogdanov
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/9ada402162ab4f38b756f30cc092c1e3
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spelling	oai:doaj.org-article:9ada402162ab4f38b756f30cc092c1e32021-11-25T06:19:05ZActivation of GABA(A) receptors inhibits T cell proliferation.1932-620310.1371/journal.pone.0251632https://doaj.org/article/9ada402162ab4f38b756f30cc092c1e32021-01-01T00:00:00Zhttps://doi.org/10.1371/journal.pone.0251632https://doaj.org/toc/1932-6203<h4>Background</h4>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.<h4>Methods</h4>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.<h4>Results</h4>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.<h4>Conclusions</h4>We conclude that activation of GABA(A)Rs provides immunosuppression by inhibiting T cell proliferation.Emma L SparrowSonya JamesKhiyam HussainStephen A BeersMark S CraggYury D BogdanovPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 16, Iss 5, p e0251632 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Emma L Sparrow Sonya James Khiyam Hussain Stephen A Beers Mark S Cragg Yury D Bogdanov Activation of GABA(A) receptors inhibits T cell proliferation.
description	<h4>Background</h4>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.<h4>Methods</h4>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.<h4>Results</h4>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.<h4>Conclusions</h4>We conclude that activation of GABA(A)Rs provides immunosuppression by inhibiting T cell proliferation.
format	article
author	Emma L Sparrow Sonya James Khiyam Hussain Stephen A Beers Mark S Cragg Yury D Bogdanov
author_facet	Emma L Sparrow Sonya James Khiyam Hussain Stephen A Beers Mark S Cragg Yury D Bogdanov
author_sort	Emma L Sparrow
title	Activation of GABA(A) receptors inhibits T cell proliferation.
title_short	Activation of GABA(A) receptors inhibits T cell proliferation.
title_full	Activation of GABA(A) receptors inhibits T cell proliferation.
title_fullStr	Activation of GABA(A) receptors inhibits T cell proliferation.
title_full_unstemmed	Activation of GABA(A) receptors inhibits T cell proliferation.
title_sort	activation of gaba(a) receptors inhibits t cell proliferation.
publisher	Public Library of Science (PLoS)
publishDate	2021
url	https://doaj.org/article/9ada402162ab4f38b756f30cc092c1e3
work_keys_str_mv	AT emmalsparrow activationofgabaareceptorsinhibitstcellproliferation AT sonyajames activationofgabaareceptorsinhibitstcellproliferation AT khiyamhussain activationofgabaareceptorsinhibitstcellproliferation AT stephenabeers activationofgabaareceptorsinhibitstcellproliferation AT markscragg activationofgabaareceptorsinhibitstcellproliferation AT yurydbogdanov activationofgabaareceptorsinhibitstcellproliferation
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Activation of GABA(A) receptors inhibits T cell proliferation.

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