title: Th22 cells are an important source of IL-22 for host protection against enteropathogenic bacteria.
abstract: Interleukin-22 (IL-22) is central to host protection against bacterial infections at barrier sites. Both innate lymphoid cells (ILCs) and T cells produce IL-22. However, the specific contributions of CD4(+) T cells and their developmental origins are unclear. We found that the enteric pathogen Citrobacter rodentium induced sequential waves of IL-22-producing ILCs and CD4(+) T cells that were each critical to host defense during a primary infection. Whereas IL-22 production by ILCs was strictly IL-23 dependent, development of IL-22-producing CD4(+) T cells occurred via an IL-6-dependent mechanism that was augmented by, but not dependent on, IL-23 and was dependent on both transcription factors T-bet and AhR. Transfer of CD4(+) T cells differentiated with IL-6 in the absence of TGF-β ("Th22" cells) conferred complete protection of infected IL-22-deficient mice whereas transferred Th17 cells did not. These findings establish Th22 cells as an important component of mucosal antimicrobial host defense.
authors.affiliation: Department of Pathology, University of Alabama at Birmingham, Birmingham, AL 35294, USA.
authors.forename: Rajatava
authors.initials: R
authors.lastname: Basu
authors.forename: Darrell B
authors.initials: DB
authors.lastname: O'Quinn
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Silberger
authors.forename: Trenton R
authors.initials: TR
authors.lastname: Schoeb
authors.forename: Lynette
authors.initials: L
authors.lastname: Fouser
authors.forename: Wenjun
authors.initials: W
authors.lastname: Ouyang
authors.forename: Robin D
authors.initials: RD
authors.lastname: Hatton
authors.forename: Casey T
authors.initials: CT
authors.lastname: Weaver
mesh_terms: D000818:Animals; D044082:Citrobacter rodentium / Q000276:immunology*; D004756:Enterobacteriaceae Infections / Q000276:immunology* / Q000401:mortality / Q000517:prevention & control; D005786:Gene Expression Regulation; D018836:Inflammation Mediators / Q000276:immunology / Q000378:metabolism; D053759:Interleukin-23 / Q000276:immunology / Q000378:metabolism; D015850:Interleukin-6 / Q000276:immunology / Q000378:metabolism; D007378:Interleukins / Q000378:metabolism / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D009092:Mucous Membrane / Q000276:immunology / Q000382:microbiology; D057132:Nuclear Receptor Subfamily 1, Group F, Member 3 / Q000235:genetics / Q000276:immunology; D018336:Receptors, Aryl Hydrocarbon / Q000235:genetics / Q000276:immunology; D020825:T-Box Domain Proteins / Q000235:genetics / Q000276:immunology; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology* / Q000378:metabolism; D058504:Th17 Cells / Q000276:immunology / Q000378:metabolism; D000097043:Interleukin-22; D000098815:T-bet Transcription Factor
chemical_list: D018836:Inflammation Mediators; D053759:Interleukin-23; D015850:Interleukin-6; D007378:Interleukins; D057132:Nuclear Receptor Subfamily 1, Group F, Member 3; D018336:Receptors, Aryl Hydrocarbon; D020825:T-Box Domain Proteins; D000097043:Interleukin-22; D000098815:T-bet Transcription Factor