The increased expression of IL-23 in inflammatory bowel disease promotes intraepithelial and lamina propria lymphocyte inflammatory responses and cytotoxicity

J Leukoc Biol. 2011 Apr;89(4):597-606. doi: 10.1189/jlb.0810456. Epub 2011 Jan 7.


This study analyzed IL-23p19 expression in inflamed mucosa of IBD and the role in the induction of IEL and NK cell activation as well as Th17 cell differentiation. Expression of IL-23p19 was performed by immunohistochemistry and quantitative real-time PCR. Expression of IL-23R was assessed by flow cytometry. Cytolytic activities of IEL and NK cells by IL-23 were determined by a standard (51)Cr-release assay. Cytokine levels were analyzed by ELISA and quantitative real-time PCR. Expression of IL-23p19 was increased significantly in inflamed mucosa of CD compared with that in UC and healthy controls. Double-staining confirmed that IL-23p19(+) cells were mainly CD68(+) macrophages/DCs. IL-23R(+) cells were increased significantly in PB- and LP-CD4(+) and -CD8(+) T and NK cells. IL-23 markedly promoted IBD IEL and NK cell activation and cytotoxicity and triggered IBD PB- and LP-T cells to secrete significantly higher levels of IFN-γ, TNF, IL-2, and IL-17A compared with controls. Importantly, IL-23 promoted IBD PB- or LP-CD4(+) T cells to differentiate into Th17 cells, characterized by increased expression of IL-17A and RORC. Anti-TNF treatment could markedly reduce IL-23 expression and Th17 cell infiltration in inflamed mucosa of CD patients. These data indicate that IL-23 is highly expressed in inflamed mucosa of IBD and plays an important role in the induction of IEL, NK, and T cell activation, proinflammatory cytokine secretion, and Th17 cell differentiation. Targeted therapy directed against IL-23p19 may have a therapeutic role in treatment of IBD.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Apoptosis
  • Blotting, Western
  • Case-Control Studies
  • Cell Differentiation
  • Cells, Cultured
  • Colitis, Ulcerative / immunology
  • Colitis, Ulcerative / metabolism*
  • Crohn Disease / immunology
  • Crohn Disease / metabolism*
  • Cytokines / metabolism
  • Female
  • Flow Cytometry
  • Humans
  • Immunoenzyme Techniques
  • Interleukin-17 / metabolism
  • Interleukin-2 / metabolism
  • Interleukin-23 Subunit p19 / genetics
  • Interleukin-23 Subunit p19 / metabolism*
  • Intestinal Mucosa / immunology*
  • Intestinal Mucosa / metabolism
  • Killer Cells, Natural / immunology
  • Killer Cells, Natural / metabolism
  • Lymphocyte Activation
  • Lymphocytes / immunology*
  • Lymphocytes / metabolism
  • Male
  • Mucous Membrane / immunology*
  • Mucous Membrane / metabolism
  • RNA, Messenger / genetics
  • Reverse Transcriptase Polymerase Chain Reaction
  • Th17 Cells


  • Cytokines
  • Interleukin-17
  • Interleukin-2
  • Interleukin-23 Subunit p19
  • RNA, Messenger