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Dissection of the microRNA transcriptomes of CD4+ T cell subsets in autoimmune ...
Cunha, Carolina; Romero, Paula Vargas; Inácio, Daniel; Pais, Ana Teresa; Pelicano, Catarina; Costa, Marina; Mensurado, Sofia; Gonçalves-Sousa, NatachaMicroRNAs (miRNAs) are key regulators of CD4+ T cell differentiation, but how they contribute to the course of an autoimmune disease in vivo remains poorly studied. Given the known roles in autoimmunity of pro-inflammatory T helper 1 (Th)1 and Th17 cells, and anti-inflammatory Foxp3+ regulatory cells, we established a triple reporter mouse for Ifng, Il17 and Foxp3, and subjected it to experimental autoimmune en...
Sustained macrophage reprogramming is required for CD8+ T cell–dependent long-t...
Jardim, Carolina; Bica, Marta; Reis-Sobreiro, Mariana; Mota, Afonso Teixeira da; Lopes, Raquel; Ferreira-Pinto, Miguel Alexandre; Sousa, Neuza S.Tumor-associated macrophages (TAM) exhibit a dual role in tumor progression and antitumor immunity. However, understanding the functional states and molecular mechanisms of antitumor TAMs remains a challenge. Herein, we show that intratumoral administration of a combination of agonists against TLR3 and CD40 [hereafter termed myeloid cell treatment (MCT)] reprogrammed TAMs in situ to adopt a protective antitumor...
Maternal γδ T cells shape offspring pulmonary type 2 immunity in a microbiota-d...
Papotto, Pedro H.; Yilmaz, Bahtiyar; Pimenta, Gonçalo; Mensurado, Sofia; Cunha, Carolina; Fiala, Gina; Gomes Da Costa, Daniel; Gonçalves-Sousa, NatachaImmune development is profoundly influenced by vertically transferred cues. However, little is known about how maternal innate-like lymphocytes regulate offspring immunity. Here, we show that mice born from γδ T cell-deficient (TCRδ-/-) dams display an increase in first-breath-induced inflammation, with a pulmonary milieu selectively enriched in type 2 cytokines and type 2-polarized immune cells, when compared ...
Primary tumors limit metastasis formation through induction of IL15-mediated cr...
Kubo, Hiroshi; Mensurado, Sofia; Gonçalves-Sousa, Natacha; Serre, Karine; Silva-Santos, BrunoMetastases are responsible for the vast majority of cancer-related deaths. Although tumor cells can become invasive early during cancer progression, metastases formation typically occurs as a late event. How the immune response to primary tumors may dictate this outcome remains poorly understood, which hampers our capacity to manipulate it therapeutically. Here, we used a two-step experimental model, based on t...
Cutting Edge : adaptive versus innate receptor signals selectively control the ...
Ribot, Julie C.; Chaves-Ferreira, Miguel; d'Orey, Francisco; Wencker, Mélanie; Gonçalves-Sousa, Natacha; Decalf, Jérémie; Simas, J Pedroγβ T lymphocytes are commonly viewed as embracing properties of both adaptive and innate immunity. Contributing to this is their responsiveness to pathogen products, either with or without the involvement of the TCR and its coreceptors. This study clarifies this paradoxical behavior by showing that these two modes of responsiveness are the properties of two discrete sets of murine lymphoid γβ T cells. Thus, MyD...
Inhibition of murine γδ lymphocyte expansion and effector function by regulator...
Gonçalves-Sousa, Natacha; Ribot, Julie C.; Barros, Ana de; Correia, Daniel V.; Caramalho, Íris; Silva-Santos, Brunoγδ T cells are highly cytolytic lymphocytes that produce large amounts of pro-inflammatory cytokines during immune responses to multiple pathogens. Furthermore, their ability to kill tumor cells has fueled the development of γδ-T-cell-based cancer therapies. Thus, the regulation of γδ-T-cell activity is of great biological and clinical relevance. Here, we show that murine CD4+CD25+ αβ T cells, the vast majority...