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Increased GABA(A) channel subunits expression in CD8(+) but not in CD4(+) T cells in BB rats developing diabetes compared to their congenic littermates
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Physiology.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Physiology.
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2011 (English)In: Molecular Immunology, ISSN 0161-5890, E-ISSN 1872-9142, Vol. 48, no 4, p. 399-407Article in journal (Refereed) Published
Abstract [en]

GABA (γ-aminobutyric acid), the main inhibitory neurotransmitter in the central nervous system is also present in the pancreatic islet β cells where it may function as a paracrine molecule and perhaps as an immunomodulator of lymphocytes infiltrating the pancreatic islet. We examined CD4(+) and CD8(+) T cells from diabetes prone (DR(lyp/lyp)) or resistant (DR(+/+)) congenic biobreeding (BB) rats for expression of GABA(A) channels. Our results show that BB rat CD4(+) and CD8(+) T cells express α1, α2, α3, α4, α6, β3, γ1, δ, ρ1 and ρ2 GABA(A) channel subunits. In CD8(+) T cells from DR(lyp/lyp) animals the subunits were significantly upregulated relative to expression levels in the CD8(+) T cells from DR(+/+) rats as well as from CD4(+) T cells from both DR(lyp/lyp) and DR(+/+) rats. Functional channels were formed in the T cells and physiological concentrations of GABA (100 nM) decreased T cell proliferation. Our results are consistent with the hypothesis that GABA in the islets of Langerhans may diminish inflammation by inhibition of activated T lymphocytes.

Place, publisher, year, edition, pages
2011. Vol. 48, no 4, p. 399-407
Keywords [en]
Diabetes, GABA, GABAA subunits, Immunomodulation, Lymphocytes, Proliferation
National Category
Medical and Health Sciences
Research subject
Physiology
Identifiers
URN: urn:nbn:se:uu:diva-148237DOI: 10.1016/j.molimm.2010.08.005ISI: 000286955400004PubMedID: 21112637OAI: oai:DiVA.org:uu-148237DiVA, id: diva2:401609
Available from: 2011-03-03 Created: 2011-03-03 Last updated: 2017-12-11Bibliographically approved
In thesis
1. Role of GABA and GABAA Channels in T lymphocytes and Stem cells
Open this publication in new window or tab >>Role of GABA and GABAA Channels in T lymphocytes and Stem cells
2012 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

GABA (gamma-aminobutyric acid) is best known for its physiological function in the central nervous system.  In the brain GABA is the main inhibitory neurotransmitter where it decreases excitability of neurons and neuronal networks.  The balance between excitation evoked by glutamate and inhibition evoked by GABA is the base from where the brain works. It is fair to say that glutamate is like the gas-pedal and GABA the brake that keeps the brain running at a normal speed.  But, it is not only in the brain that GABA is taking a part in a physiological process vital to life. GABA is present in blood and is even released in the pancreatic islets. What function GABA has in these tissues is still being examined and is the focus of this thesis. The GABA concentration in the peripheral tissues is in the submicromolar concentration range. 

The studies in this thesis support the idea that GABA reduces the proliferation and cytokine secretion from immune cells by activating high-affinity GABAA channels in the cells. In contrast, in retinal progenitor stem cells GABA promotes cell proliferation.  These studies demonstrate that the effect of GABA on proliferation is cell-type specific. The GABAA channel subunit isoforms expressed in human, mice and rats T cells differ between the species.  This interspecies variability will result in different pharmacological profile of the subtypes of GABAA channels expressed whereas the physiological process most likely is the same.  Clearly, GABA is not only a neurotransmitter molecule but is also an immunomodulator and an important signal molecule in peripheral tissues. 

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2012. p. 60
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 768
National Category
Neurosciences Physiology
Identifiers
urn:nbn:se:uu:diva-172541 (URN)978-91-554-8348-7 (ISBN)
Public defence
2012-05-28, C4 :301, BMC, Husargatan 3, Uppsala, 13:00 (English)
Supervisors
Available from: 2012-05-07 Created: 2012-04-11 Last updated: 2018-01-12Bibliographically approved

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Mendu, Suresh KumarJin, ZheBirnir, Bryndis

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