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Immunologic Research
Published in: Immunologic Research 2-3/2019

01-06-2019 | Prazosin | Original Article

Noradrenaline modulates CD4+ T cell priming in rat experimental autoimmune encephalomyelitis: a role for the α1-adrenoceptor

Authors: Ivan Pilipović, Ivana Vujnović, Zorica Stojić-Vukanić, Raisa Petrović, Duško Kosec, Mirjana Nacka-Aleksić, Nebojša Jasnić, Gordana Leposavić

Published in: Immunologic Research | Issue 2-3/2019

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Abstract

Pharmacological blockade of α1-adrenoceptor is shown to influence development of experimental autoimmune encephalomyelitis (EAE), an IL-17-producing CD4+TCR+ (Th17) cell-mediated disease mimicking multiple sclerosis. Considering significance of CD4+ cell priming for the clinical outcome of EAE, the study examined α1-adrenoceptor-mediated influence of catecholamines, particularly those derived from draining lymph node (dLN) cells (as catecholamine supply from nerve fibers decreases with the initiation of autoimmune diseases) for CD4+ cell priming. The results confirmed diminishing effect of immunization on nerve fiber-derived noradrenaline supply and showed that antigen presenting and CD4+ cells synthesize catecholamines, while antigen presenting cells and only CD4+CD25+Foxp3+ regulatory T cells (Tregs) express α1-adrenoceptor. The analysis of influence of α1-adrenoceptor antagonist prazosin on the myelin basic protein (MBP)-stimulated CD4+ lymphocytes in dLN cell culture showed their diminished proliferation in the presence of prazosin. This was consistent with prazosin enhancing effect on Treg frequency and their Foxp3 expression in these cultures. The latter was associated with upregulation of TGF-β expression. Additionally, prazosin decreased antigen presenting cell activation and affected their cytokine profile by diminishing the frequency of cells that produce Th17 polarizing cytokines (IL-1β and IL-23) and increasing that of IL-10-producing cells. Consistently, the frequency of all IL-17A+ cells and those co-expressing GM-CSF within CD4+ lymphocytes was decreased in prazosin-supplemented MBP-stimulated dLN cell cultures. Collectively, the results indicated that dLN cell-derived catecholamines may influence EAE development by modulating interactions between distinct subtypes of CD4+ T cells and antigen presenting cells through α1-adrenoceptor and consequently CD4+ T cell priming.
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Metadata
Title
Noradrenaline modulates CD4+ T cell priming in rat experimental autoimmune encephalomyelitis: a role for the α1-adrenoceptor
Authors
Ivan Pilipović
Ivana Vujnović
Zorica Stojić-Vukanić
Raisa Petrović
Duško Kosec
Mirjana Nacka-Aleksić
Nebojša Jasnić
Gordana Leposavić
Publication date
01-06-2019
Publisher
Springer US
Keyword
Prazosin
Published in
Immunologic Research / Issue 2-3/2019
Print ISSN: 0257-277X
Electronic ISSN: 1559-0755
DOI
https://doi.org/10.1007/s12026-019-09082-y

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