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Human intraepithelial lymphocytes

Mucosal Immunology (2018) | Download Citation

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Abstract

The location of intraepithelial lymphocytes (IEL) between epithelial cells, their effector memory, cytolytic and inflammatory phenotype positions them to kill infected epithelial cells and protect the intestine against pathogens. Human TCRαβ+CD8αβ+ IEL have the dual capacity to recognize modified self via natural killer (NK) receptors (autoreactivity) as well as foreign antigen via the T cell receptor (TCR), which is accomplished in mouse by two cell subsets, the naturally occurring TCRαβ+CD8αα+ and adaptively induced TCRαβ+CD8αβ+ IEL subsets, respectively. The private/oligoclonal nature of the TCR repertoire of both human and mouse IEL suggests local environmental factors dictate the specificity of IEL responses. The line between sensing of foreign antigens and autoreactivity is blurred for IEL in celiac disease, where recognition of stress ligands by induced activating NK receptors in conjunction with inflammatory signals such as IL-15 can result in low-affinity TCR/non-cognate antigen and NK receptor/stress ligand interactions triggering destruction of intestinal epithelial cells.

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Acknowledgements

Support for this work was provided by grants from the US National Institutes of Health (RO1DK67180 and R01DK098435) and Digestive Diseases Research Core Center at the University of Chicago (DK42086). We would like to thank Valérie Abadie for contributions made to figure art and design and Jordan D. Ernest for assistance with experiments. A special thanks to Zachery M. Earley, Sangman M. Kim, and Marlies Meisel for sharing various data and ideas on mouse IEL that were critical to establishing comparisons between human and mouse. Finally, we are thankful to the human subjects providing us with material to examine human IEL.

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  1. Department of Medicine, University of Chicago, Chicago, USA

    • Toufic Mayassi
    •  & Bana Jabri
  2. Committee on Immunology, University of Chicago, Chicago, USA

    • Toufic Mayassi
    •  & Bana Jabri
  3. Department of Pathology, University of Chicago, Chicago, USA

    • Bana Jabri
  4. Department of Pediatrics, University of Chicago, Chicago, USA

    • Bana Jabri

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Contributions

T.M. and B.J. designed experiments. T.M. conducted experiments. T.M. and B.J. designed figures. T.M. and B.J. wrote the manuscript.

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The authors declare no competing interests.

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Correspondence to Bana Jabri.

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https://doi.org/10.1038/s41385-018-0016-5