Tomados em conjunto, os resultados obtidos no presente estudo são indicativos de que a via de sinalização mTOR está envolvida no mecanismo de ação da cloroquina sobre células dendríticas, uma vez que:
1. Ocorre aumento da expressão de mTOR fosforilada em células dendríticas tratadas com cloroquina.
2. O bloqueio da via de sinalização mTOR, com o inibidor rapamicina, reverteu os efeitos da cloroquina sobre a indução do perfil tolerogênico das células dendríticas e sobre a capacidade dessas células induzirem diminuição da proliferação de células T e sua diferenciação em células com perfil regulador.
3. O bloqueio da via mTOR inibiu a eficácia terapêutica das DCs moduladas com CQ observado pelo aumento da inflamação no Sistema Nervoso Central de animais portadores de Encefalomielite Autoimune Experimental.
Neste projeto mostramos que a via metabólica de sinalização intracelular mTOR é regulada em células dendríticas tratadas com a cloroquina, posicionando esta via como participante do mecanismo de indução de tolerância imunológica. Estes achados revelam o potencial de manipulação sobre esta via no sentido de desenvolvimento de estratégias terapêuticas eficazes no controle das respostas inflamatórias.
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