Enterocytes, fibroblasts and myeloid cells synergize in anti-bacterial and anti-viral pathways with IL22 as the central cytokine

Authors Jean Paul ten Klooster, Marianne Bol-Schoenmakers, Kitty van Summeren, Arno van Vliet, Cornelis de Haan, Frank van Kuppeveld, Saertje Verkoeijen, Raymond Pieters
Published in Communications biology
Publication date 2021
Research groups Innovative Testing in Life Sciences and Chemistry
Type Article

Summary

IL22 is an important cytokine involved in the intestinal defense mechanisms against microbiome. By using ileum-derived organoids, we show that the expression of anti-microbial peptides (AMPs) and anti-viral peptides (AVPs) can be induced by IL22. In addition, we identified a bacterial and a viral route, both leading to IL22 production by T cells, but via different pathways. Bacterial products, such as LPS, induce enterocyte-secreted SAA1, which triggers the secretion of IL6 in fibroblasts, and subsequently IL22 in T cells. This IL22 induction can then be enhanced by macrophage-derived TNFα in two ways: by enhancing the responsiveness of T cells to IL6 and by increasing the expression of IL6 by fibroblasts. Viral infections of intestinal cells induce IFNβ1 and subsequently IL7. IFNβ1 can induce the expression of IL6 in fibroblasts and the combined activity of IL6 and IL7 can then induce IL22 expression in T cells. We also show that IL22 reduces the expression of viral entry receptors (e.g. ACE2, TMPRSS2, DPP4, CD46 and TNFRSF14), increases the expression of anti-viral proteins (e.g. RSAD2, AOS, ISG20 and Mx1) and, consequently, reduces the viral infection of neighboring cells. Overall, our data indicates that IL22 contributes to the innate responses against both bacteria and viruses.

On this publication contributed

  • Jean Paul ten Klooster | Researcher | Research group Innovative Testing in Life Sciences and Chemistry
    Jean Paul ten Klooster
    • Researcher
    • Research group: Innovative Testing in Life Sciences and Chemistry
  • Kitty van Summeren | Researcher | Research group Innovative Testing in Life Sciences & Chemistry
    Kitty van Summeren
    • Researcher
    • Research group: Innovative Testing in Life Sciences and Chemistry
  • Raymond Pieters | Professor | Research group Innovative Testing in Life Sciences & Chemistry
    Raymond Pieters
    • Professor
    • Research group: Innovative Testing in Life Sciences and Chemistry

Language English
Published in Communications biology
Year and volume 4 1
Key words anti-bacterial agents, cytokines, enterocytes, immunology, fibroblasts, interleukins, anti-viral agents
Digital Object Identifier 10.1038/s42003-021-02176-0

Jean Paul ten Klooster

Jean Paul ten Klooster | Researcher | Research group Innovative Testing in Life Sciences and Chemistry

Jean Paul ten Klooster

  • Researcher
  • Research group: Innovative Testing in Life Sciences and Chemistry