title: Interleukin-22 induces interleukin-18 expression from epithelial cells during intestinal infection.
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.
authors: Institute of Microbiology and Hygiene, Charité - University Medicine Berlin, Berlin 12203, Germany.
authors: Melba
authors: M
authors: Muñoz
authors: Immunology Department, Genentech, Inc., South San Francisco, CA 94080, USA.
authors: Celine
authors: C
authors: Eidenschenk
authors: Immunology Department, Genentech, Inc., South San Francisco, CA 94080, USA.
authors: Naruhisa
authors: N
authors: Ota
authors: Immunology Department, Genentech, Inc., South San Francisco, CA 94080, USA.
authors: Kit
authors: K
authors: Wong
authors: Institute of Microbiology and Hygiene, Charité - University Medicine Berlin, Berlin 12203, Germany.
authors: Uwe
authors: U
authors: Lohmann
authors: Department of Medicine I for Gastroenterology, Infectious Disease and Rheumatology and Research Center ImmunoSciences (RCIS), Charité - University Medicine Berlin, Berlin 12203, Germany.
authors: Anja A
authors: AA
authors: Kühl
authors: Immunology Department, Genentech, Inc., South San Francisco, CA 94080, USA.
authors: Xiaoting
authors: X
authors: Wang
authors: Immunology Department, Genentech, Inc., South San Francisco, CA 94080, USA.
authors: Paolo
authors: P
authors: Manzanillo
authors: Immunology Department, Genentech, Inc., South San Francisco, CA 94080, USA.
authors: Yun
authors: Y
authors: Li
authors: Immunology Department, Genentech, Inc., South San Francisco, CA 94080, USA.
authors: Sascha
authors: S
authors: Rutz
authors: Immunology Department, Genentech, Inc., South San Francisco, CA 94080, USA.
authors: Yan
authors: Y
authors: Zheng
authors: Pathology Department, Genentech, Inc., South San Francisco, CA 94080, USA.
authors: Lauri
authors: L
authors: Diehl
authors: Physiological Chemistry Department, Genentech, Inc., South San Francisco, CA 94080, USA.
authors: Nobuhiko
authors: N
authors: Kayagaki
authors: Immunology Department, Genentech, Inc., South San Francisco, CA 94080, USA.
authors: Menno
authors: M
authors: van Lookeren-Campagne
authors: Institute of Microbiology and Hygiene, Charité - University Medicine Berlin, Berlin 12203, Germany.
authors: Oliver
authors: O
authors: Liesenfeld
authors: Institute of Microbiology and Hygiene, Charité - University Medicine Berlin, Berlin 12203, Germany.
authors: Markus
authors: M
authors: Heimesaat
authors: Immunology Department, Genentech, Inc., South San Francisco, CA 94080, USA. Electronic address: ouyang@gene.com.
authors: Wenjun
authors: W
authors: Ouyang
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D044082:Citrobacter rodentium / Q000276:immunology; D004756:Enterobacteriaceae Infections / Q000276:immunology* / Q000382:microbiology; D004847:Epithelial Cells / Q000276:immunology; D007079:Ileitis / Q000276:immunology / Q000382:microbiology / Q000469:parasitology; D007082:Ileum / Q000276:immunology / Q000382:microbiology / Q000469:parasitology; D007249:Inflammation / Q000276:immunology; D007371:Interferon-gamma / Q000096:biosynthesis; D020382:Interleukin-18 / Q000096:biosynthesis / Q000276:immunology*; D007378:Interleukins / Q000235:genetics / Q000276:immunology*; D007413:Intestinal Mucosa / Q000276:immunology* / Q000382:microbiology / Q000469:parasitology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D020556:Neutrophil Infiltration / Q000276:immunology; D009504:Neutrophils / Q000276:immunology; D009924:Organ Culture Techniques; D012333:RNA, Messenger / Q000096:biosynthesis; D018417:Th1 Cells / Q000276:immunology; D014122:Toxoplasma / Q000276:immunology; D014123:Toxoplasmosis / Q000276:immunology* / Q000469:parasitology; D015854:Up-Regulation; D000097043:Interleukin-22
chemical_list: D007371:Interferon-gamma; D020382:Interleukin-18; D007378:Interleukins; D012333:RNA, Messenger; D000097043:Interleukin-22