Details

Autor(en) / Beteiligte

• Zaph, Colby
• Troy, Amy E.
• Taylor, Betsy C.
• Berman-Booty, Lisa D.
• Guild, Katherine J.
• Du, Yurong
• Yost, Evan A.
• Gruber, Achim D.
• May, Michael J.
• Greten, Florian R.
• Eckmann, Lars
• Karin, Michael
• Artis, David

Titel

Epithelial cell-intrinsic IKKβ expression regulates innate and adaptive immunity in the gut (42.4)

Ist Teil von

• The Journal of immunology (1950), 2007-04, Vol.178 (1_Supplement), p.S34-S34

Erscheinungsjahr

2007

Quelle

Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals

Beschreibungen/Notizen

• 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 regulation of immunity is unknown. Here we show that IEC-intrinsic IKKβ-dependent gene expression is a critical regulator of dendritic cell (DC) and CD4+ T cell responses in the gut. Following infection with the parasite Trichuris, littermate control mice develop pathogen-specific TH2 cytokine responses and eradicate infection while mice with an IEC-specific deletion of IKKβ (IkkbΔIEC mice) fail to do so. Further, IkkbΔIEC mice exhibit exacerbated production of DC-derived IL-12/23p40 and TNF-α, heightened levels of CD4+ T cell-derived IFN-γ and IL-17, and develop severe intestinal inflammation. Blockade of proinflammatory cytokines during Trichuris infection ablates the requirement for IKKβ in IECs to promote CD4+ TH2 cell-dependent immunity, identifying a critical role for IECs in limiting type 1 cytokine production in the GI tract. These results suggest that the balance of IKKβ-dependent gene expression is critical for intestinal immune homeostasis by promoting mucosal immunity and limiting chronic inflammation. This work is funded by the NIH, CCFA and the Irvington Institute.