IL-22 Deficiency Alters Colonic Microbiota To Be Transmissible and Colitogenic

Abstract

Interleukin-22 (IL-22) is a good candidate to play a critical role in regulating gut microbiota because it is an important inducer of antimicrobial peptides and mucins in the gut. However, whether IL-22 participates into immune homeostasis by way of modulating gut microbiota remains to be elucidated. In this study, we find through 16S rRNA gene pyrosequencing analysis that healthy IL-22 deficient mice had altered colonic microbiota, notably with decreased abundance of some genera including Lactobacillus and increased levels of others. Mice harboring this altered microbiota exhibited more severe disease during experimentally-induced colitis. Interestingly, this altered gut microbiota can be transmitted to co-housed wild-type animals along with the increased susceptibility to this colitis, indicating an important role of IL-22 in shaping the homeostatic balance between immunity and colonic microbiota for host health.

Functional and phenotypic heterogeneity of group 3 innate lymphoid cells

“…Mice with disrupted ILC3‐derived IL‐22 responses exhibit altered gut microbiota and increased susceptibility to experimentally induced colitis 49, 80, 81, 82. Most notably, expansion of segmented filamentous bacteria (SFB) – a canonical Th17‐inducing commensal species – occurs in the absence of ILC3 responses 49.…”

Reciprocity in Microbiome and Immune System Interactions and its Implications in Disease and Health

“…This effect is associated with an increase in IL-22 levels and neutralization of IL-22 abolishes RegII and RegIII gene expression [72]. Mice with IL-22 deficiency demonstrate changes in gut microbiota compostion [73]. Thus, we speculate that mycobacterial adjuvant-induced IL-22 response could go through an intermediary stage for induction of Reg family of antibacterial peptides from intestinal epithelial cells that consequently changes gut microbiota in NOD mice for protection from diabetes development.…”

“…T-bet regulates production of TNF-α in dendritic cells to prevent pro-inflammatory response to gut microbiota and thus excessive production of TNF-α by colonic dendritic cells in the TRUC colitis model causes tissue injury in the colon [91]. IL-22 from different cellular sources such as innate lymphoid cells, Th17 cells and natural killer cells can have a protective role in inflammatory bowel disease [73,93,94]. IL-22 induces the expression of Reg family of antimicrobial peptides, RegIIIβ and RegIIIγ in colonic epithelial cells [95].…”

“…In the absence of antibacterial effects of IL-22, commensal bacteria can be overwhemingly expanded. IL-22 deficient mice have an altered composition of gut microbiota and demonstrate more severe colitis in an experimental mouse model [73]. Of note, the Lactobacillacae family of normal gut microflora is reduced in these mice [73].…”

“…IL-22 deficient mice have an altered composition of gut microbiota and demonstrate more severe colitis in an experimental mouse model [73]. Of note, the Lactobacillacae family of normal gut microflora is reduced in these mice [73]. Gut microbiota could be exchanged between co-housed mice because of copraphagia in mice.…”