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Immunity. 2015 Feb 17;42(2):321-331. doi: 10.1016/j.immuni.2015.01.011. Epub 2015 Feb 10.

Interleukin-22 induces interleukin-18 expression from epithelial cells during intestinal infection.

Author information

1
Institute of Microbiology and Hygiene, Charité - University Medicine Berlin, Berlin 12203, Germany.
2
Immunology Department, Genentech, Inc., South San Francisco, CA 94080, USA.
3
Department of Medicine I for Gastroenterology, Infectious Disease and Rheumatology and Research Center ImmunoSciences (RCIS), Charité - University Medicine Berlin, Berlin 12203, Germany.
4
Pathology Department, Genentech, Inc., South San Francisco, CA 94080, USA.
5
Physiological Chemistry Department, Genentech, Inc., South San Francisco, CA 94080, USA.
6
Immunology Department, Genentech, Inc., South San Francisco, CA 94080, USA. Electronic address: ouyang@gene.com.

Abstract

T helper 1 (Th1) cell-associated immunity exacerbates ileitis induced by oral Toxoplasma gondii infection. We show here that attenuated ileitis observed in interleukin-22 (IL-22)-deficient mice was associated with reduced production of Th1-cell-promoting IL-18. IL-22 not only augmented the expression of Il18 mRNA and inactive precursor protein (proIL-18) in intestinal epithelial cells after T. gondii or Citrobacter rodentium infection, but also maintained the homeostatic amount of proIL-18 in the ileum. IL-22, however, did not induce the processing to active IL-18, suggesting a two-step regulation of IL-18 in these cells. Although IL-18 exerted pathogenic functions during ileitis triggered by T. gondii, it was required for host defense against C. rodentium. Conversely, IL-18 was required for the expression of IL-22 in innate lymphoid cells (ILCs) upon T. gondii infection. Our results define IL-18 as an IL-22 target gene in epithelial cells and describe a complex mutual regulation of both cytokines during intestinal infection.

PMID:
25680273
DOI:
10.1016/j.immuni.2015.01.011
[Indexed for MEDLINE]
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