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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Public Library of Science (PLoS)
2021-01-01
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| Series: | PLoS ONE |
| Online Access: | https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0251632&type=printable |
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| 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 |
| collection | DOAJ |
| 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 |
| id | doaj-art-9ada402162ab4f38b756f30cc092c1e3 |
| institution | Kabale University |
| issn | 1932-6203 |
| language | English |
| publishDate | 2021-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj-art-9ada402162ab4f38b756f30cc092c1e32025-08-20T03:25:34ZengPublic Library of Science (PLoS)PLoS ONE1932-62032021-01-01165e025163210.1371/journal.pone.0251632Activation of GABA(A) receptors inhibits T cell proliferation.Emma L SparrowSonya JamesKhiyam HussainStephen A BeersMark S CraggYury D Bogdanov<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.https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0251632&type=printable |
| spellingShingle | 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. PLoS ONE |
| title | 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_short | Activation of GABA(A) receptors inhibits T cell proliferation. |
| title_sort | activation of gaba a receptors inhibits t cell proliferation |
| url | https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0251632&type=printable |
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