Samenvatting

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.