The Journal of clinical investigation, Jan 2, 2015
Accumulation of IL-17-producing Th17 cells is associated with the development of multiple autoimm... more Accumulation of IL-17-producing Th17 cells is associated with the development of multiple autoimmune diseases; however, the contribution of microRNA (miRNA) pathways to the intrinsic control of Th17 development remains unclear. Here, we demonstrated that miR-21 expression is elevated in Th17 cells and that mice lacking miR-21 have a defect in Th17 differentiation and are resistant to experimental autoimmune encephalomyelitis (EAE). Furthermore, we determined that miR-21 promotes Th17 differentiation by targeting and depleting SMAD-7, a negative regulator of TGF-β signaling. Moreover, the decreases in Th17 differentiation in miR-21-deficient T cells were associated with defects in SMAD-2/3 activation and IL-2 suppression. Finally, we found that treatment of WT mice with an anti-miR-21 oligonucleotide reduced the clinical severity of EAE, which was associated with a decrease in Th17 cells. Thus, we have characterized a T cell-intrinsic miRNA pathway that enhances TGF-β signaling, limi...
The immune system is usually seen as a collection of independent (specific) lymphocyte clones. Ra... more The immune system is usually seen as a collection of independent (specific) lymphocyte clones. Randomly generated and activated at random, these lymphocytes follow only their individual, clonal history. Thus, in traditional descriptions, immunological activity is neither systemic nor historical and is never “physiological”. However, recent descriptions show an abundant “auto”- reactivity in healthy organisms, an evidence of internal connectivity. The two major sources of immunogenic contacts, namely, dietary proteins and products of the autochthonous microbiota fail to induce progressive “secondary-type” clonal expansions (or “memory”). Natural IgM may arise in “antigen-free” organisms as they do in conventionally raised animals; actually, clonal receptors of both T and B lymphocytes are formed in antigen-free intracellular environments and are not driven by antigen exposure. Early in ontogenesis natural immunoglobulins are organized in characteristic patterns of reactivity which ar...
The solar cell market is dominated by cells based on silicon wafers. However, due to the high mat... more The solar cell market is dominated by cells based on silicon wafers. However, due to the high materials costs and new concepts such as building-integrated architecture, other technologies have been implemented, some of these being the “second generation” thin-film approaches based on different materials. 1 The one with the best reported performance is CuIn1− xGaxSe2 (CIGS), for which efficiencies of 20. 3% have been measured in the laboratory. 2 However, due to the low availability of In and Ga in the Earth's crust, the ...
The Journal of clinical investigation, Jan 2, 2015
Accumulation of IL-17-producing Th17 cells is associated with the development of multiple autoimm... more Accumulation of IL-17-producing Th17 cells is associated with the development of multiple autoimmune diseases; however, the contribution of microRNA (miRNA) pathways to the intrinsic control of Th17 development remains unclear. Here, we demonstrated that miR-21 expression is elevated in Th17 cells and that mice lacking miR-21 have a defect in Th17 differentiation and are resistant to experimental autoimmune encephalomyelitis (EAE). Furthermore, we determined that miR-21 promotes Th17 differentiation by targeting and depleting SMAD-7, a negative regulator of TGF-β signaling. Moreover, the decreases in Th17 differentiation in miR-21-deficient T cells were associated with defects in SMAD-2/3 activation and IL-2 suppression. Finally, we found that treatment of WT mice with an anti-miR-21 oligonucleotide reduced the clinical severity of EAE, which was associated with a decrease in Th17 cells. Thus, we have characterized a T cell-intrinsic miRNA pathway that enhances TGF-β signaling, limi...
The immune system is usually seen as a collection of independent (specific) lymphocyte clones. Ra... more The immune system is usually seen as a collection of independent (specific) lymphocyte clones. Randomly generated and activated at random, these lymphocytes follow only their individual, clonal history. Thus, in traditional descriptions, immunological activity is neither systemic nor historical and is never “physiological”. However, recent descriptions show an abundant “auto”- reactivity in healthy organisms, an evidence of internal connectivity. The two major sources of immunogenic contacts, namely, dietary proteins and products of the autochthonous microbiota fail to induce progressive “secondary-type” clonal expansions (or “memory”). Natural IgM may arise in “antigen-free” organisms as they do in conventionally raised animals; actually, clonal receptors of both T and B lymphocytes are formed in antigen-free intracellular environments and are not driven by antigen exposure. Early in ontogenesis natural immunoglobulins are organized in characteristic patterns of reactivity which ar...
The solar cell market is dominated by cells based on silicon wafers. However, due to the high mat... more The solar cell market is dominated by cells based on silicon wafers. However, due to the high materials costs and new concepts such as building-integrated architecture, other technologies have been implemented, some of these being the “second generation” thin-film approaches based on different materials. 1 The one with the best reported performance is CuIn1− xGaxSe2 (CIGS), for which efficiencies of 20. 3% have been measured in the laboratory. 2 However, due to the low availability of In and Ga in the Earth's crust, the ...
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Papers by Andre Cunha