DEWTON DE MORAES VASCONCELOS

(Fonte: Lattes)
Índice h a partir de 2011
11
Lattes
ResearcherID
ORCID
Projetos de Pesquisa
Unidades Organizacionais
Instituto Central, Hospital das Clínicas, Faculdade de Medicina - Médico
LIM/56 - Laboratório de Investigação em Dermatologia e Imunodeficiências, Hospital das Clínicas, Faculdade de Medicina
LIM/31 - Laboratório de Genética e Hematologia Molecular, Hospital das Clínicas, Faculdade de Medicina

Filtros

Mostrar mais
Limpar filtros

Configurações

Colaboração internacional: Inglaterra ×

Resultados de Busca

Agora exibindo 1 - 2 de 2
  • article 91 Citação(ões) na Scopus
    Disruption of an antimycobacterial circuit between dendritic and helper T cells in human SPPL2a deficiency
    (2018) KONG, Xiao-Fei; MARTINEZ-BARRICARTE, Ruben; KENNEDY, James; MELE, Federico; LAZAROV, Tomi; DEENICK, Elissa K.; MA, Cindy S.; BRETON, Gaelle; LUCERO, Kimberly B.; LANGLAIS, David; BOUSFIHA, Aziz; AYTEKIN, Caner; MARKLE, Janet; TROUILLET, Celine; JABOT-HANIN, Fabienne; ARLEHAMN, Cecilia S. Lindestam; RAO, Geetha; PICARD, Capucine; LASSEAU, Theo; LATORRE, Daniela; HAMBLETON, Sophie; DESWARTE, Caroline; ITAN, Yuval; ABARCA, Katia; MORAES-VASCONCELOS, Dewton; AILAL, Fatima; IKINCIOGULLARI, Aydan; DOGU, Figen; BENHSAIEN, Ibtihal; SETTE, Alessandro; ABEL, Laurent; BOISSON-DUPUIS, Stephanie; SCHROEDER, Bernd; NUSSENZWEIG, Michel C.; LIU, Kang; GEISSMANN, Frederic; TANGYE, Stuart G.; GROS, Philippe; SALLUSTO, Federica; BUSTAMANTE, Jacinta; CASANOVA, Jean-Laurent
    Human inborn errors of IFN-gamma immunity underlie mycobacterial diseases. We describe patients with Mycobacterium bovis (BCG) disease who are homozygous for loss-of-function mutations of SPPL2A. This gene encodes a transmembrane protease that degrades the N-terminal fragment (NTF) of CD74 (HLA invariant chain) in antigen-presenting cells. The CD74 NTF therefore accumulates in the HLA class II+ myeloid and lymphoid cells of SPPL2a-deficient patients. This toxic fragment selectively depletes IL-12-and IL-23-producing CD1c(+) conventional dendritic cells (cDC2s) and their circulating progenitors. Moreover, SPPL2a-deficient memory T(H)1(star) cells selectively fail to produce IFN-gamma when stimulated with mycobacterial antigens in vitro. Finally, Sppl2a(-/-) mice lack cDC2s, have CD4(+) T cells that produce small amounts of IFN-gamma after BCG infection, and are highly susceptible to infection with BCG or Mycobacterium tuberculosis. These findings suggest that inherited SPPL2a deficiency in humans underlies mycobacterial disease by decreasing the numbers of cDC2s and impairing IFN-gamma production by mycobacterium-specific memory T(H)1(star) cells.
  • article 506 Citação(ões) na Scopus
    IRF8 Mutations and Human Dendritic-Cell Immunodeficiency
    (2011) HAMBLETON, Sophie; SALEM, Sandra; BUSTAMANTE, Jacinta; BIGLEY, Venetia; BOISSON-DUPUIS, Stephanie; AZEVEDO, Joana; FORTIN, Anny; HANIFFA, Muzlifah; CERON-GUTIERREZ, Lourdes; BACON, Chris M.; MENON, Geetha; TROUILLET, Celine; MCDONALD, David; CAREY, Peter; GINHOUX, Florent; ALSINA, Laia; ZUMWALT, Timothy J.; KONG, Xiao-Fei; KUMARARATNE, Dinakantha; BUTLER, Karina; HUBEAU, Marjorie; FEINBERG, Jacqueline; AL-MUHSEN, Saleh; CANT, Andrew; ABEL, Laurent; CHAUSSABEL, Damien; DOFFINGER, Rainer; TALESNIK, Eduardo; GRUMACH, Anete; DUARTE, Alberto; ABARCA, Katia; MORAES-VASCONCELOS, Dewton; BURK, David; BERGHUIS, Albert; GEISSMANN, Frederic; COLLIN, Matthew; CASANOVA, Jean-Laurent; GROS, Philippe
    BACKGROUND The genetic analysis of human primary immunodeficiencies has defined the contribution of specific cell populations and molecular pathways in the host defense against infection. Disseminated infection caused by bacille Calmette-Guerin (BCG) vaccines is an early manifestation of primary immunodeficiencies, such as severe combined immunodeficiency. In many affected persons, the cause of disseminated BCG disease is unexplained. METHODS We evaluated an infant presenting with features of severe immunodeficiency, including early-onset disseminated BCG disease, who required hematopoietic stem-cell transplantation. We also studied two otherwise healthy subjects with a history of disseminated but curable BCG disease in childhood. We characterized the monocyte and dendritic-cell compartments in these three subjects and sequenced candidate genes in which mutations could plausibly confer susceptibility to BCG disease. RESULTS We detected two distinct disease-causing mutations affecting interferon regulatory factor 8 (IRF8). Both K108E and T80A mutations impair IRF8 transcriptional activity by disrupting the interaction between IRF8 and DNA. The K108E variant was associated with an autosomal recessive severe immunodeficiency with a complete lack of circulating monocytes and dendritic cells. The T80A variant was associated with an autosomal dominant, milder immunodeficiency and a selective depletion of CD11c+CD1c+ circulating dendritic cells. CONCLUSIONS These findings define a class of human primary immunodeficiencies that affect the differentiation of mononuclear phagocytes. They also show that human IRF8 is critical for the development of monocytes and dendritic cells and for antimycobacterial immunity. (Funded by the Medical Research Council and others.)