Biliary epithelial cells regulate autoreactive T cells: Implications for biliary-specific diseases

Takashi Kamihira, Shinji Shimoda, Minoru Nakamura, Teruhumi Yokoyama, Yasushi Takii, Akira Kawano, Mizuki Handa, Hiromi Ishibashi, M. Eric Gershwin, Mine Harada

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Abstract

The biliary epithelial cell (BEC) is the target for several human immune mediated liver diseases, including primary biliary cirrhosis, but it is not always clear whether the BEC functions as an accessory cell or an antigen presenting cell, although it is well documented that BECs express high levels of human leukocyte antigen Class II, intercellular adhesion molecule-1, and lymphocyte function-associated antigen-3. To examine this issue, we established autoreactive T-cell clones from human leukocyte antigen-DR53 patients with primary biliary cirrhosis and characterized BEC function as a function of the ability of BECs to regulate T-cell activation. We report herein that BEC-mediated T-cell activation occurs partially via programmed death 1 ligands in a cell-contact-dependent manner. Further, such activation occurs via prostaglandin E2 production in a cell-contact-independent fashion. Moreover, the production of prostaglandin E2 was partially controlled by interleiikin-1β and tumor necrosis factor α. In conclusion, the regulatory activities of BECs are important for the maintenance of peripheral immune tolerance. Further, modulation of BEC function may be used for therapeutic modulation.

Original languageEnglish
Pages (from-to)151-159
Number of pages9
JournalHepatology
Volume41
Issue number1
DOIs
Publication statusPublished - Jan 1 2005

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All Science Journal Classification (ASJC) codes

  • Hepatology

Cite this

Kamihira, T., Shimoda, S., Nakamura, M., Yokoyama, T., Takii, Y., Kawano, A., ... Harada, M. (2005). Biliary epithelial cells regulate autoreactive T cells: Implications for biliary-specific diseases. Hepatology, 41(1), 151-159. https://doi.org/10.1002/hep.20494