IDDF2023-ABS-0298 Insight of interleukin-22 in protecting intestinal fibrosis: its potential influence on reducing inflammation and maintaining microbiota abundance

Background

The role of interleukin 22 (IL22) in colonic fibrosis remains largely unknown. Previous studies considered it as a double-edged sword between anti-inflammation and fibro-genesis. Therefore, we aimed to investigate the role of IL22 in inflammation-related colonic fibrosis formation.

Methods

Male C57B6/J mice aged 8 weeks (~25g) fed a standard diet and housed in pathogen-free conditions with a 12h day-night cycle were divided into the DSS group, DSS+IL22 group and control group. The two DSS groups were fed with 2% DSS for 7 days and distilled water for 14 days, repeating three times. For the administration of rIL-22, mice were given rIL-22 (200 ng/mouse) or phosphate-buffered saline intraperitoneally at 0, 2, 4, 6 days after DSS administration. Colonic bacterial 16S rRNA gene sequencing assay and RNA sequencing of colon tissue were performed.

Results

All mice survived after three cycles of 2%DSS administration and the colonic fibrosis model was successfully created and confirmed by Masson’s staining. Mice exhibited a greater reduction in body weight (P<0.0001) (IDDF2023-ABS-0298 Figure 1a) and higher disease severity score upon DSS treatment (P<0.0001) (IDDF2023-ABS-0298 Figure 1b). Colons of DSS-fed were significantly shorter than the control group (P<0.0001) (IDDF2023-ABS-0298 Figure 1c). Notably, the DSS+IL22 group exhibited a slightly longer colon length, less weight reduction and lower histopathology score (IDDF2023-ABS-0298 Figure 1d) than the DSS group (without significant change) at sacrifice. IL-22 restored colonic microbiota abundance, notably with reducing Clostridium-sensu-stricto-1 and increasing Lachnospiraceae_NK4A136 and Turicibacter (IDDF2023-ABS-0298 Figure 1e). A total of 278 genes were differentially expressed in the DSS+IL22 vs DSS group. We figured out that the 48 upregulated genes were mainly enriched in extracellular function, muscle contraction and biosynthesis (IDDF2023-ABS-0298 Figure 1f). And the 230 downregulated genes were mainly enriched in immune response (like NOD−like receptor signaling pathway and TNF signaling pathway) (IDDF2023-ABS-0298 Figure 1g).

Conclusions

We primarily revealed the potential protecting role of IL22 in colonic fibrosis with the underlying mechanism related to the maintenance of microbiota abundance and inhibition of pro-inflammatory pathways like the TNF pathway and NLR pathway.