Unique CD14 intestinal macrophages contribute to the pathogenesis of Crohn disease via IL-23/IFN-gamma axis

J Clin Invest. 2008 Jun;118(6):2269-80. doi: 10.1172/JCI34610.


Intestinal macrophages play a central role in regulation of immune responses against commensal bacteria. In general, intestinal macrophages lack the expression of innate-immune receptor CD14 and do not produce proinflammatory cytokines against commensal bacteria. In this study, we identified what we believe to be a unique macrophage subset in human intestine. This subset expressed both macrophage (CD14, CD33, CD68) and DC markers (CD205, CD209) and produced larger amounts of proinflammatory cytokines, such as IL-23, TNF-alpha, and IL-6, than typical intestinal resident macrophages (CD14-CD33+ macrophages). In patients with Crohn disease (CD), the number of these CD14+ macrophages were significantly increased compared with normal control subjects. In addition to increased numbers of cells, these cells also produced larger amounts of IL-23 and TNF-alpha compared with those in normal controls or patients with ulcerative colitis. In addition, the CD14+ macrophages contributed to IFN-gamma production rather than IL-17 production by lamina propria mononuclear cells (LPMCs) dependent on IL-23 and TNF-alpha. Furthermore, the IFN-gamma produced by LPMCs triggered further abnormal macrophage differentiation with an IL-23-hyperproducing phenotype. Collectively, these data suggest that this IL-23/IFN-gamma-positive feedback loop induced by abnormal intestinal macrophages contributes to the pathogenesis of chronic intestinal inflammation in patients with CD.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antigens, CD / biosynthesis
  • Antigens, Differentiation, Myelomonocytic / biosynthesis
  • Cell Differentiation
  • Cell Separation
  • Crohn Disease / genetics*
  • Crohn Disease / metabolism
  • Flow Cytometry
  • Humans
  • Inflammation
  • Interferon-gamma / metabolism*
  • Interleukin-23 / metabolism*
  • Intestinal Mucosa / pathology
  • Lipopolysaccharide Receptors / biosynthesis*
  • Macrophages / metabolism*
  • Models, Biological
  • Monocytes / metabolism
  • Mucous Membrane / metabolism
  • Sialic Acid Binding Ig-like Lectin 3


  • Antigens, CD
  • Antigens, Differentiation, Myelomonocytic
  • CD33 protein, human
  • Interleukin-23
  • Lipopolysaccharide Receptors
  • Sialic Acid Binding Ig-like Lectin 3
  • Interferon-gamma