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Alteration of intestinal epithelial function by intraepithelial lymphocyte homing

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Abstract

Background

Intimate cross-talk may take place between intestinal epithelial cells and intraepithelial lymphocytes (IEL). The purpose of this study was to analyze the influence of lymphocyte migration into the epithelium on epithelial function, using an in vitro “IEL homing” model.

Methods

Molecular expression on epithelial cells was analyzed by flow cytometry. The barrier function of the epithelial monolayer was assessed by transepithelial electrical resistance. Cytokine production was measured by enzyme-linked immunosorbent assay (ELISA).

Results

(1) IEL homing into the epithelia induced significant phenotypic changes in epithelial cells; upregulation of MHC class I, and II, intercellular adhesion molecule (ICAM)-1, and CD44. IEL-derived interferon-γ (IFN-γ) could partially account for this alteration, as a neutralizing antibody (Ab) against IFN-γ inhibited the upregulation of these molecules, except for CD44. (2) A marked fall in transepithelial electrical resistance was observed 4 h after IEL homing started, and Ab against IFN-γ slightly inhibited this fall in resistance. (3) The production of interleukin (IL)-8 and IFN-γ inducible protein-10 (IP-10), but not transforming growth factor (TGF)-β1 or tumor necrosis factor (TNF)-α, in the epithelial monolayer was markedly induced after IEL homing in a basolaterally polarized fashion. IEL-conditioned media also induced the production of these cytokines in epithelial cells, thus suggesting that IEL-derived soluble factor(s) induce epithelial chemokine production.

Conclusions

Under inflammatory conditions, IEL obviously interact with epithelial cells and upregulate adhesion molecules, alter barrier function, and enhance chemokine production. Because such alterations may increase epithelial permeability to luminal antigens or accelerate the migration of other inflammatory cells, our results suggest that IEL have a critical role in mucosal immunity.

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Authors and Affiliations

  1. Department of Gastroenterology, Institute of Clinical Medicine, University of Tsukuba, 1-1-1 Tennoudai, Tsukuba, 305-8575, Japan

    Takeshi Shibahara, Kaori Miyazaki, Daisuke Sato, Hirohumi Matsui, Akinori Yanaka, Akira Nakahara & Naomi Tanaka

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  1. Takeshi Shibahara
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  2. Kaori Miyazaki
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  3. Daisuke Sato
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  5. Akinori Yanaka
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  6. Akira Nakahara
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Shibahara, T., Miyazaki, K., Sato, D. et al. Alteration of intestinal epithelial function by intraepithelial lymphocyte homing. J Gastroenterol 40, 878–886 (2005). https://doi.org/10.1007/s00535-005-1631-y

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  • DOI: https://doi.org/10.1007/s00535-005-1631-y

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