RESUMEN
The intestines have the essential but challenging mission of absorbing nutrients, restricting damage from food-derived toxins, promoting colonization by symbionts, and expelling pathogens. These processes are often incompatible with each other and must therefore be prioritized in view of the most crucial contemporary needs of the host. Recent work has shown that tissue-resident innate lymphoid cells (ILCs) constitute a central sensory module allowing adaptation of intestinal organ function to changing environmental input. Here, we propose a conceptual framework positing that the various types of ILC act in distinct modules with intestinal epithelial cells, collectively safeguarding organ function. Such homeostasis-promoting circuitry has high potential to be plumbed for new therapeutic approaches to the treatment of immune-mediated inflammatory diseases.
Asunto(s)
Células Epiteliales/inmunología , Homeostasis/inmunología , Inmunidad Innata/inmunología , Mucosa Intestinal/inmunología , Linfocitos/inmunología , Animales , Citocinas/inmunología , Citocinas/metabolismo , Células Epiteliales/metabolismo , Humanos , Mucosa Intestinal/citología , Mucosa Intestinal/metabolismo , Linfocitos/metabolismo , Tejido Linfoide/citología , Tejido Linfoide/inmunología , Tejido Linfoide/metabolismo , Modelos InmunológicosRESUMEN
An amendment to this paper has been published and can be accessed via a link at the top of the paper.
RESUMEN
IL-22 has dual functions during tumorigenesis. Short term IL-22 production protects against genotoxic stress, whereas uncontrolled IL-22 activity promotes tumor growth; therefore, tight regulation of IL-22 is essential. TGF-ß1 promotes the differentiation of Th17 cells, which are known to be a major source of IL-22, but the effect of TGF-ß signaling on the production of IL-22 in CD4+ T cells is controversial. Here we show an increased presence of IL-17+IL-22+ cells and TGF-ß1 in colorectal cancer compared to normal adjacent tissue, whereas the frequency of IL-22 single producing cells is not changed. Accordingly, TGF-ß signaling in CD4+ T cells (specifically Th17 cells) promotes the emergence of IL-22-producing Th17 cells and thereby tumorigenesis in mice. IL-22 single producing T cells, however, are not dependent on TGF-ß signaling. We show that TGF-ß, via AhR induction, and PI3K signaling promotes IL-22 production in Th17 cells.