title: Transcription factor c-Rel plays a crucial role in driving anti-CD40-mediated innate colitis.
abstract: Genetic and environmental factors, including the commensal microbiota, have a crucial role in the development of inflammatory bowel disease. Aberrant activation of the transcription factor NF-κB is associated with chronic intestinal inflammation in mice and humans. Recently, an emerging family of innate lymphoid cells (ILCs) has been identified at mucosal sites contributing to the maintenance of gut homeostasis and intestinal immunopathology. Here, we show that the NF-κB protein c-Rel regulates the inflammatory potential of colonic IFN-γ(+)Thy1(+) ILCs to induce anti-CD40-mediated colitis in rag1(-/-) mice. Stimulation of dendritic cells (DCs) with anti-CD40 or CD40L led to translocation of c-Rel into the nucleus resulting in induction of expression of interleukin-12 (IL-12) and IL-23, key regulators of innate cell-induced colitis. While c-Rel deficiency completely abrogated anti-CD40-induced colitis, adoptively transferred wild-type DCs were able to induce pronounced colonic inflammation in rag1(-/-)rel(-/-) mice. In summary, these results suggest that the expression of c-Rel in DCs is essential for initiating anti-CD40-mediated intestinal pathogenesis.
authors.affiliation: 1] Institute for Medical Microbiology and Hygiene, Philipps University of Marburg, Marburg, Germany [2] Max Planck Institute for Infection Biology, Department of Immunology, Berlin, Germany.
authors.forename: A
authors.initials: A
authors.lastname: Visekruna
authors.affiliation: Institute for Medical Microbiology and Hygiene, Philipps University of Marburg, Marburg, Germany.
authors.forename: T
authors.initials: T
authors.lastname: Linnerz
authors.affiliation: Institute for Medical Microbiology and Hygiene, Philipps University of Marburg, Marburg, Germany.
authors.forename: V
authors.initials: V
authors.lastname: Martinic
authors.affiliation: Institute for Medical Microbiology and Hygiene, Philipps University of Marburg, Marburg, Germany.
authors.forename: N
authors.initials: N
authors.lastname: Vachharajani
authors.affiliation: Institute for Medical Microbiology and Hygiene, Philipps University of Marburg, Marburg, Germany.
authors.forename: S
authors.initials: S
authors.lastname: Hartmann
authors.affiliation: Institute of Laboratory Medicine and Pathobiochemistry, Molecular Diagnostics, Philipps University of Marburg, Marburg, Germany.
authors.forename: H
authors.initials: H
authors.lastname: Harb
authors.affiliation: 1] Max Planck Institute for Infection Biology, Department of Immunology, Berlin, Germany [2] Immunology Section, Department of Experimental Medical Science, Lund University, Lund, Sweden.
authors.forename: T
authors.initials: T
authors.lastname: Joeris
authors.affiliation: Max Planck Institute for Infection Biology, Department of Immunology, Berlin, Germany.
authors.forename: P I
authors.initials: PI
authors.lastname: Pfefferle
authors.affiliation: 1] Department of Neuropathology, Philipps University of Marburg, Marburg, Germany [2] School of Molecular Bioscience, The University of Sydney, Darlington, New South Wales, Australia.
authors.forename: M J
authors.initials: MJ
authors.lastname: Hofer
authors.affiliation: 1] Institute for Medical Microbiology and Hygiene, Philipps University of Marburg, Marburg, Germany [2] Max Planck Institute for Infection Biology, Department of Immunology, Berlin, Germany.
authors.forename: U
authors.initials: U
authors.lastname: Steinhoff
mesh_terms: D000818:Animals; D019013:CD40 Antigens / Q000276:immunology*; D003092:Colitis / Q000235:genetics* / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D016207:Cytokines / Q000378:metabolism; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism; D004195:Disease Models, Animal; D006801:Humans; D007113:Immunity, Innate; D018836:Inflammation Mediators / Q000378:metabolism; D007371:Interferon-gamma / Q000378:metabolism; D008214:Lymphocytes / Q000276:immunology / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D016328:NF-kappa B / Q000378:metabolism; D011485:Protein Binding; D020569:Proto-Oncogene Proteins c-rel / Q000235:genetics* / Q000378:metabolism; D015398:Signal Transduction; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism
chemical_list: D019013:CD40 Antigens; D016207:Cytokines; D018836:Inflammation Mediators; D016328:NF-kappa B; D020569:Proto-Oncogene Proteins c-rel; D014157:Transcription Factors; D007371:Interferon-gamma
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