Repository logo

Browsing by Author "Ribot, Julie C."

Now showing 1 - 2 of 2
  • MicroRNA‐181a restricts human γδ T cell differentiation by targeting Map3k2 and Notch2
    Publication . Gordino, Gisela; Costa‐Pereira, Sara; Corredeira, Patrícia; Alves, Patrícia; Costa, Luís; Gomes, Anita Q.; Silva‐Santos, Bruno; Ribot, Julie C.
    γδ T cells are a conserved population of lymphocytes that contributes to anti-tumor responses through its overt type 1 inflammatory and cytotoxic properties. We have previously shown that human γδ T cells acquire this profile upon stimulation with IL-2 or IL-15, in a differentiation process dependent on MAPK/ERK signaling. Here, we identify microRNA-181a as a key modulator of human γδ T cell differentiation. We observe that miR-181a is highly expressed in patients with prostate cancer and that this pattern is associated with lower expression of NKG2D, a critical mediator of cancer surveillance. Interestingly, miR-181a expression negatively correlates with an activated type 1 effector profile obtained from in vitro differentiated γδ T cells and miR-181a overexpression restricts their levels of NKG2D and TNF-α. Upon in silico analysis, we identify two miR-181a candidate targets, Map3k2 and Notch2, which we validate via overexpression coupled with luciferase assays. These results reveal a novel role for miR-181a as a critical regulator of human γδ T cell differentiation and highlight its potential for manipulation of γδ T cells in next-generation immunotherapies.
    2022-01Journal article Open access Show more
  • γδ-T cells promote IFN-γ–dependent Plasmodium pathogenesis upon liver-stage infection
    Publication . Ribot, Julie C.; Neres, Rita; Zuzarte-Luís, Vanessa; Gomes, Anita Quintal; Mancio-Silva, Liliana; Mensurado, Sofia; Pinto-Neves, Daniel; Santos, Miguel M.; Carvalho, Tânia; Landry, Jonathan J. M.; Rolo, Eva A.; Malik, Ankita; Silva, Daniel Varón; Mota, Maria M.; Silva-Santos, Bruno; Pamplona, Ana
    Cerebral malaria (CM) is a major cause of death due to Plasmodium infection. Both parasite and host factors contribute to the onset of CM, but the precise cellular and molecular mechanisms that contribute to its pathogenesis remain poorly characterized. Unlike conventional αβ-T cells, previous studies on murine γδ-T cells failed to identify a nonredundant role for this T cell subset in experimental cerebral malaria (ECM). Here we show that mice lacking γδ-T cells are resistant to ECM when infected with Plasmodium berghei ANKA sporozoites, the liver-infective form of the parasite and the natural route of infection, in contrast with their susceptible phenotype if challenged with P. berghei ANKA-infected red blood cells that bypass the liver stage of infection. Strikingly, the presence of γδ-T cells enhanced the expression of Plasmodium immunogenic factors and exacerbated subsequent systemic and brain-infiltrating inflammatory αβ-T cell responses. These phenomena were dependent on the proinflammatory cytokine IFN-γ, which was required during liver stage for modulation of the parasite transcriptome, as well as for downstream immune-mediated pathology. Our work reveals an unanticipated critical role of γδ-T cells in the development of ECM upon Plasmodium liver-stage infection.
    2019-04Journal article Restricted access Show more