γδ intraepithelial lymphocytes drive tumor necrosis factor-α responsiveness to intestinal iron challenge: Relevance to hemochromatosis

Amy E. Ten Elshof, Gary M. Brittenham, Karen A. Chorney, Michael J. Page, Glenn Gerhard, Edward E. Cable, Michael J. Chorney

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Abstract

The dependence of intestinal epithelial cell (IEC) growth and differentiation on intraepithelial lymphocytes (IELs) expressing the gamma/delta (γδ) T-cell receptor (TCR), suggested a potential role for γδ+ IELs in the regulation of iron absorption. We therefore examined the levels of hepatic iron and the IEL cytokine responses in C57BL/6J control and class I and TCR knockout lines (placed on a C57BL/6J genetic background) following the administration of supplemental dietary iron. The highest level of liver iron was found in the β2-microglobulin knockout (β2m(-/-)) mice followed by the TCR-δ knockout (TCRδ(-/-)) animals. TCR-α knockout (TCRα(-/-)) and control animals did not differ in their iron levels. Liver iron loading correlated inversely with the ability of the mice to generate an IEL tumor necrosis factor (TNF)-α response. These observations suggest a model in which IEC iron loading is communicated to IELs via the HFE class I protein. The result of this communication is the initiation of TNF-α release by γδ+ IELs (sustained by macrophages and dendritic cells) contributing to the upregulation of ferritin expression and possibly to the normal maintenance of the IEC apoptotic pathway.

Original languageEnglish (US)
Pages (from-to)223-232
Number of pages10
JournalImmunological Reviews
Volume167
StatePublished - Apr 26 1999

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All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology

Cite this

Ten Elshof, A. E., Brittenham, G. M., Chorney, K. A., Page, M. J., Gerhard, G., Cable, E. E., & Chorney, M. J. (1999). γδ intraepithelial lymphocytes drive tumor necrosis factor-α responsiveness to intestinal iron challenge: Relevance to hemochromatosis. Immunological Reviews, 167, 223-232.