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Exacerbated experimental colitis in TNFAIP8-deficient mice.

Honghong Sun1, Yunwei Lou2, Thomas Porturas1

  • 1Department of Pathology and Laboratory Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, 19104;

Journal of Immunology (Baltimore, Md. : 1950)
|May 8, 2015
PubMed
Summary

TNF-α-induced protein 8 (TIPE) deficiency exacerbates colon inflammation. TIPE is crucial for maintaining colon homeostasis and protecting against colitis, impacting cell death and proliferation.

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Area of Science:

  • Immunology
  • Gastroenterology
  • Molecular Biology

Background:

  • TNF-α-induced protein 8 (TNFAIP8 or TIPE) is linked to cancer and bacterial infections.
  • Its precise roles in physiology and pathology remain largely unknown.
  • Elevated TIPE expression is observed in various human cancers.

Purpose of the Study:

  • To investigate the function of TIPE in the context of colonic inflammation.
  • To generate and characterize TIPE-deficient mice to study its role in gut homeostasis.

Main Methods:

  • Generation of TIPE-deficient mice using germ line gene targeting.
  • Induction of colitis using dextran sodium sulfate (DSS) in wild-type and TIPE-deficient mice.
  • Analysis of clinical signs, leukocyte infiltration, bacterial load, cytokine production, and cell proliferation/death.

Main Results:

  • TIPE-deficient mice exhibited increased sensitivity to DSS-induced colitis, with reduced survival and greater weight loss.
  • Exacerbated inflammation was characterized by enhanced leukocyte infiltration, bacterial invasion, and inflammatory cytokine production.
  • Bone marrow chimeric experiments identified nonhematopoietic cells as critical for TIPE's protective role.
  • TIPE-deficient intestinal epithelial cells showed increased cell death and reduced proliferation.

Conclusions:

  • TIPE plays a significant role in maintaining colon homeostasis.
  • TIPE is essential for protecting the colon against inflammatory conditions like colitis.
  • Nonhematopoietic TIPE is crucial for mitigating colonic inflammation and maintaining intestinal epithelial integrity.