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Strain specific maturation of Dendritic cells and production of IL-1ß controls CD40-driven colitis.
Ogrinc Wagner, Ana; Friedrich, Verena; Barthels, Christian; Marconi, Peggy; Blutke, Andreas; Brombacher, Frank; Brocker, Thomas.
Afiliación
  • Ogrinc Wagner A; Institute for Immunology, Faculty of Medicine, Ludwig-Maximilians-Universität München, Planegg-Martinsried, Germany.
  • Friedrich V; Institute for Immunology, Faculty of Medicine, Ludwig-Maximilians-Universität München, Planegg-Martinsried, Germany.
  • Barthels C; Institute for Immunology, Faculty of Medicine, Ludwig-Maximilians-Universität München, Planegg-Martinsried, Germany.
  • Marconi P; Department of Chemical and Pharmaceutical Sciences, University of Ferrara, Ferrara, Italy.
  • Blutke A; Research Unit Analytical Pathology, Helmholtz Zentrum München, Neuherberg, Germany.
  • Brombacher F; Division of Immunology, University of Cape Town & South African Medical Research Council, Cape Town, South Africa.
  • Brocker T; International Centre for Genetic Engineering and Biotechnology, Cape Town component, South Africa.
PLoS One ; 14(1): e0210998, 2019.
Article en En | MEDLINE | ID: mdl-30653608
Intestinal integrity is maintained by balanced numbers of CD103+ Dendritic cells (DCs), which generate peripherally induced regulatory T cells (iTregs). We have developed a mouse model where DC-specific constitutive CD40 signals caused a strong reduction of CD103+ DCs in the lamina propria (LP) and intestinal lymph nodes (LN). As a consequence, also iTregs were strongly reduced and transgenic mice on the C57Bl/6-background (B6) developed fatal colitis. Here we describe that transgenic mice on a pure Balb/c-background (B/c) do not show any pathologies, while transgenic C57Bl/6 x Balb/c (F1) mice develop weak colon inflammation, without fatal colitis. This graded pathology correlated with the effects of CD40-signalling on DCs in each background, with striking loss of CD103+ DCs in B6, but reduced in F1 and diminished in B/c background. We further show direct correlation of CD103+ DC-numbers with numbers of iTregs, the frequencies of which behave correspondingly. Striking effects on B6-DCs reflected robust loss of surface MHCII, known to be crucial for iTreg induction. Furthermore, elevated levels of IL-23 together with IL-1, found only in B6 mice, support generation of intestinal IFN-γ+IL-17+ Th17 cells and IFN-γ+ Th1 cells, responsible for onset of disease. Together, this demonstrates a novel aspect of colitis-control, depending on genetic background. Moreover, strain-specific environmental sensing might alter the CD103+ DC/iTreg-axis to tip intestinal homeostatic balance to pathology.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Células Dendríticas / Colitis / Antígenos CD40 / Interleucina-1beta Tipo de estudio: Prognostic_studies Límite: Animals Idioma: En Revista: PLoS One Asunto de la revista: CIENCIA / MEDICINA Año: 2019 Tipo del documento: Article País de afiliación: Alemania Pais de publicación: Estados Unidos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Células Dendríticas / Colitis / Antígenos CD40 / Interleucina-1beta Tipo de estudio: Prognostic_studies Límite: Animals Idioma: En Revista: PLoS One Asunto de la revista: CIENCIA / MEDICINA Año: 2019 Tipo del documento: Article País de afiliación: Alemania Pais de publicación: Estados Unidos