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Thèse de Doctorat
DOI
10.11606/T.42.2017.tde-08052017-153614
Document
Auteur
Nom complet
Cristiano Rossato
Unité de l'USP
Domain de Connaissance
Date de Soutenance
Editeur
São Paulo, 2016
Directeur
Jury
Peron, Jean Pierre Schatzmann (Président)
Almeida, Rafael Ribeiro
Britto, Luiz Roberto Giorgetti de
Mendes, Joao Gustavo Pessini Amarante
Pinto, Frederico Azevedo da Costa
Titre en portugais
Estudo do papel do receptor ionotrópico de glutamato NMDAR na imunomodulação da encefalomielite experimental autoimune.
Mots-clés en portugais
Encefalomielite experimental autoimune
Linfócitos T
MK801
NMDAR
Receptores de glutamato
Resumé en portugais
As células T exercem papel crucial nas respostas imunes adaptativas e em doenças autoimunes, como a esclerose múltipla. O glutamato, neurotransmissor mais abundante no SNC, age por meio de duas famílias de receptores: metabotrópico e ionotrópico. As células T são alvo do glutamato durante a ativação e apresentação de antígenos, pois está presente nas sinapses imunológicas, porém, pouco se sabe a respeito de seu papel na função das células T. Nós estudamos o papel do NMDAR nas respostas mediadas por células T. In vitro, o uso do antagonista MK801 reduziu a linfoproliferação e a síntese de IFN-γ e IL-17A, bem com o NMDA reduziu a proliferação e produção de IFN-γ e IL-17A. In vivo, o MK801 reduziu a gravidade da EAE, resultado da menor infiltração de linfócitos Th1 e Th17 no SNC. Além disso, o MK801 reduziu a expressão de Rorc, Il17a, Stat4, Ccr4, Ccr6 e Ifna2 no SNC. Em suma, esses dados confirmam que o NMDAR exerce papel nas funções mediadas por células T, indicando que as células T são alvos do excesso do glutamato via NMDAR em doenças neuroinflamatórias.
Titre en anglais
Study of the role of glutamate ionotropic receptor NMDAR in the immunomodulation of experimental autoimmune encephalomyelitis.
Mots-clés en anglais
Experimental autoimmune encephalomyelitis
Glutamate receptors
MK801
NMDAR
T Lymphocytes
Resumé en anglais
T cells play a crucial role in adaptive immune responses and autoimmune diseases, such as multiple sclerosis. Glutamate is the most abundant neurotransmitter in the CNS, and it acts through two receptor families: metabotropic and ionotropic. T cells are target of glutamate during activation and antigen presentation, because glutamate is also present in the immunological synapses, however, little is known about its role on T cell functions. We investigated the role of NMDAR in immune-mediated T cell responses. In vitro, the use of the antagonist MK801 reduced T cell proliferation and cytokine production (IFN-γ e IL-17A), as well as NMDA reduced lymphocyte proliferation and IFN-γ e IL-17A production, in a dose dependent manner. In vivo, MK801 diminished severity of EAE, result of the minor Th1 and Th17 infiltration in the CNS. In addition, MK801 reduced Rorc, Il17a, Stat4, Ccr4, Ccr6 and Ifna2 expression in the CNS. In short, our data confirm that the NMDAR play a role in T cell-mediated functions, indicating that T cells are target of glutamate excess via NMDAR in neuroinflammatory diseases.
 
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Date de Publication
2017-05-08
 
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