Chloroquine-treated dendritic cells require STAT1 signaling for their tolerogenic activity

Autor(es)

Thome, Rodolfo ^{[1, 2]} ; Bonfanti, Amanda Pires ^[1] ; Rasouli, Javad ^[2] ; Mari, Elisabeth Rose ^[2] ; Zhang, Guang-Xian ^[2] ; Rostami, Abdolmohamad ^[2] ; Verinaud, Liana ^[1]

Afiliação do(s) autor(es)

^[1] Univ Estadual Campinas, Dept Struct & Funct Biol, Inst Biol, UNICAMP, Campinas, SP - Brazil

^[2] Thomas Jefferson Univ, Dept Neurol, Philadelphia, PA 19107 - USA

• Tipo de documento: Artigo Científico
• Fonte: European Journal of Immunology; v. 48, n. 7, p. 1228-1234, JUL 2018.
• Citações Web of Science: 3

Resumo

MS and EAE are Tcell-driven autoimmune diseases of the CNS where IL-17-producing Th17 cells promote damage and are pathogenic. Conversely, tolerogenic DCs induce Tregcells and suppress Th17 cells. Chloroquine (CQ) suppresses EAE through the modulation of DCs by unknown mechanisms. Here, we show that STAT 1 is necessary for CQ-induced tolerogenic DCs (tolDCs) to efficiently suppress EAE. We observed that CQ induces phosphorylation of STAT1 in DCs in vivo and in vitro. Genetic blockage of STAT1 abrogated the suppressive activity of CQ-treated DCs. Opposed to its WT counterparts, CQ-treated STAT1(-/-) BMDCs were unable to suppress Th17 cells and increased EAE severity. Our findings show that STAT1 is a major signaling pathway in CQ-induced tolDCs and may shed light on new therapeutic avenues for the induction of tolDCs in autoimmune diseases such as MS. (AU)

• Processo FAPESP: 14/19492-3 - Influência das vias de sinalização mTOR, STAT1/3 e iNOS na atividade de células dendríticas tolerogênicas
• Beneficiário: Liana Maria Cardoso Verinaud
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 14/02631-0 - Papel do óxido nítrico (NO) na modulação da encefalomielite autoimune experimental (EAE) após transferência adotiva de células dendríticas tolerogênicas: influência dos eixos MyD88-mTOR-iNOS e STAT1/3-iNOS
• Beneficiário: Rodolfo Thomé
• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado