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CD44 deficiency attenuates chronic murine ileitis.

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|October 16, 2008
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CD44 plays a key role in chronic small intestinal inflammation, particularly in CD4(+) T cells, influencing the development of ileitis in a tumor necrosis factor (TNF)-driven model.

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Area of Science:

  • Immunology
  • Gastroenterology
  • Molecular Biology

Background:

  • Lymphocyte recruitment is crucial for inflammatory responses.
  • CD44 is an adhesion molecule involved in lymphocyte trafficking.

Purpose of the Study:

  • To investigate the role of CD44 in the development of chronic small intestinal inflammation in vivo.
  • To analyze CD44's function in a tumor necrosis factor (TNF)-driven model of ileitis.

Main Methods:

  • Utilized a TNF-driven model of chronic ileitis (TNFΔARE mice).
  • Assessed CD44 and hyaluronan expression and function using ELISA, RT-PCR, immunohistochemistry, and flow cytometry.
  • Conducted adoptive transfer studies and analyzed CD44-deficient mice.

Main Results:

  • Increased hyaluronan and CD44 expression, particularly variant 7, on CD4(+) T cells in TNFΔARE mice.
  • CD44 colocalized with α4β7 integrin, linking lymphocyte rolling and arrest.
  • CD4(+) T cells conferred ileitis, and CD44 deficiency attenuated disease severity.

Conclusions:

  • CD44 on CD4(+) and CD8(+) T cells is important for TNF-mediated ileitis development.
  • Findings highlight CD44's critical role in chronic intestinal inflammation.