Epithelial-cell-intrinsic IKK-β expression regulates intestinal immune homeostasis

Colby Zaph, Amy E. Troy, Betsy C. Taylor, Lisa D. Berman-Booty, Katherine J. Guild, Yurong Du, Evan A. Yost, Achim D. Gruber, Michael J. May, Florian R. Greten, Lars Eckmann, Michael Karin and David Artis ()
Additional contact information
Colby Zaph: Department of Pathobiology and,
Amy E. Troy: Department of Pathobiology and,
Betsy C. Taylor: Department of Pathobiology and,
Lisa D. Berman-Booty: Department of Pathobiology and,
Katherine J. Guild: Department of Pathobiology and,
Yurong Du: Department of Pathobiology and,
Evan A. Yost: Department of Pathobiology and,
Achim D. Gruber: Free University Berlin, 14163 Berlin, Germany
Michael J. May: University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA
Florian R. Greten: Laboratory of Gene Regulation and Signal Transduction, and
Lars Eckmann: University of California San Diego, La Jolla, California 92093, USA
Michael Karin: Laboratory of Gene Regulation and Signal Transduction, and
David Artis: Department of Pathobiology and,

Nature, 2007, vol. 446, issue 7135, 552-556

Abstract: Abstract Intestinal epithelial cells (IECs) provide a primary physical barrier against commensal and pathogenic microorganisms in the gastrointestinal (GI) tract, but the influence of IECs on the development and regulation of immunity to infection is unknown1. Here we show that IEC-intrinsic IκB kinase (IKK)-β-dependent gene expression is a critical regulator of responses of dendritic cells and CD4+ T cells in the GI tract. Mice with an IEC-specific deletion of IKK-β show a reduced expression of the epithelial-cell-restricted cytokine thymic stromal lymphopoietin in the intestine and, after infection with the gut-dwelling parasite Trichuris, fail to develop a pathogen-specific CD4+ T helper type 2 (TH2) response and are unable to eradicate infection. Further, these animals show exacerbated production of dendritic-cell-derived interleukin-12/23p40 and tumour necrosis factor-α, increased levels of CD4+ T-cell-derived interferon-γ and interleukin-17, and develop severe intestinal inflammation. Blockade of proinflammatory cytokines during Trichuris infection ablates the requirement for IKK-β in IECs to promote CD4+ TH2 cell-dependent immunity, identifying an essential function for IECs in tissue-specific conditioning of dendritic cells and limiting type 1 cytokine production in the GI tract. These results indicate that the balance of IKK-β-dependent gene expression in the intestinal epithelium is crucial in intestinal immune homeostasis by promoting mucosal immunity and limiting chronic inflammation.

Date: 2007
References: Add references at CitEc
Citations: View citations in EconPapers (1)

Downloads: (external link)
https://www.nature.com/articles/nature05590 Abstract (text/html)
Access to the full text of the articles in this series is restricted.

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:nature:v:446:y:2007:i:7135:d:10.1038_nature05590

Ordering information: This journal article can be ordered from
https://www.nature.com/

DOI: 10.1038/nature05590

Access Statistics for this article

Nature is currently edited by Magdalena Skipper

More articles in Nature from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().