Assuntos
Alérgenos/imunologia , Dermatite Atópica/imunologia , Proteínas de Peixes da Dieta/imunologia , Hipersensibilidade Alimentar/imunologia , Cadeias Pesadas de Miosina/imunologia , Salmão/imunologia , Adolescente , Animais , Criança , Pré-Escolar , Dermatite Atópica/sangue , Dermatite Atópica/diagnóstico , Feminino , Proteínas de Peixes da Dieta/isolamento & purificação , Hipersensibilidade Alimentar/sangue , Hipersensibilidade Alimentar/diagnóstico , Humanos , Imunoglobulina E/imunologia , Japão , Masculino , Cadeias Pesadas de Miosina/genética , Cadeias Pesadas de Miosina/isolamento & purificação , Proteínas Recombinantes/genética , Proteínas Recombinantes/imunologia , Proteínas Recombinantes/isolamento & purificação , Testes Sorológicos , Índice de Gravidade de Doença , Testes CutâneosRESUMO
Transfer of type-1 helper T-conditioned (Th1-conditioned) cells promotes functional recovery with enhanced axonal remodeling after spinal cord injury (SCI). This study explored the molecular mechanisms underlying the beneficial effects of pro-inflammatory Th1-conditioned cells after SCI. The effect of Th1-conditioned cells from interferon-γ (ifn-γ) knockout mice (ifn-γ(-/-) Th1 cells) on the recovery after SCI was reduced. Transfer of Th1-conditioned cells led to the activation of microglia (MG) and macrophages (MΦs), with interleukin 10 (IL-10) upregulation. This upregulation of IL-10 was reduced when ifn-γ(-/-) Th1 cells were transferred. Intrathecal neutralization of IL-10 in the spinal cord attenuated the effects of Th1-conditioned cells. Further, IL-10 is robustly secreted from Th1-conditioned cells in an ifn-γ-dependent manner. Th1-conditioned cells from interleukin 10 knockout (il-10(-/-)) mice had no effects on recovery from SCI. These findings demonstrate that ifn-γ-dependent secretion of IL-10 from Th1 cells, as well as native MG/MΦs, is required for the promotion of motor recovery after SCI.
Assuntos
Interferon gama/fisiologia , Interleucina-10/metabolismo , Macrófagos/metabolismo , Microglia/metabolismo , Traumatismos da Medula Espinal/terapia , Células Th1/metabolismo , Transferência Adotiva , Animais , Células Cultivadas , Feminino , Fator Neurotrófico Derivado de Linhagem de Célula Glial/metabolismo , Imunoterapia Adotiva , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Fatores de Crescimento Neural/metabolismo , Recuperação de Função Fisiológica , Traumatismos da Medula Espinal/imunologia , Células Th1/transplante , Regulação para CimaRESUMO
The role of T lymphocytes in central nervous system (CNS) injuries is controversial, with inconsistent results reported concerning the effects of T-lymphocyte transfer on spinal cord injury (SCI). Here, we demonstrate that a specific T-lymphocyte subset enhances functional recovery after contusion SCI in mice. Intraperitoneal adoptive transfer of type 1 helper T (Th1)-conditioned cells 4 days after SCI promoted recovery of locomotor activity and tactile sensation and concomitantly induced regrowth of corticospinal tract and serotonergic fibers. However, neither type 2 helper T (Th2)- nor IL-17-producing helper T (Th17)-conditioned cells had such effects. Activation of microglia and macrophages were observed in the spinal cords of Th1-transfered mice after SCI. Specifically, M2 subtype of microglia/macrophages was upregulated after Th1 cell transfer. Neutralization of interleukin 10 secreted by Th1-conditioned cells significantly attenuated the beneficial effects by Th1-conditioned lymphocytes after SCI. We also found that Th1-conditioned lymphocytes secreted significantly higher levels of neurotrophic factor, neurotrophin 3 (NT-3), than Th2- or Th17-conditioned cells. Thus, adoptive transfer of pro-inflammatory Th1-conditioned cells has neuroprotective effects after SCI, with prospective implications in immunomodulatory treatment of CNS injury.
