Significance of immunoglobulin G4 (IgG4)-positive cells in extrahepatic cholangiocarcinoma: Molecular mechanism of IgG4 reaction in cancer tissue

フォーマット:

論文

責任表示:

Harada, Kenichi ; Shimoda, Shinji ; Kimura, Yasushi ; Sato, Yasunori ; Ikeda, Hiroko ; Igarashi, Saya ; Ren, Xiang-Shan ; Sato, Hirohide ; Nakanuma, Yasuni

言語:

英語

出版情報:

American Association for the Study of Liver Diseases / Wiley-Blackwell, 2012-07-01

著者名:

Harada, Kenichi

Shimoda, Shinji

Kimura, Yasushi

Sato, Yasunori

Ikeda, Hiroko

Igarashi, Saya

Ren, Xiang-Shan

Sato, Hirohide

Nakanuma, Yasuni

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掲載情報:

Hepatology

ISSN:

0270-9139      

巻:

56

通号:

1

開始ページ:

157

終了ページ:

164

バージョン:

author

概要:

IgG4 reactions consisting of marked infiltration by immunoglobulin G4 (IgG4)-positive plasma cells in affected organs is found in cancer patients as well as patients with IgG4-related diseases. Notably, extrahepatic cholangiocarcinomas accompanying marked IgG4 reactions clinicopathologically mimic IgG4-related sclerosing cholangitis. The regulatory cytokine interleukin (IL)-10 is thought to induce the differentiation of IgG4-positive cells. In this … study, to clarify the mechanism of the IgG4 reaction in extrahepatic cholangiocarcinoma, we investigated nonprofessional antigen-presenting cells (APCs) generating IL-10-producing regulatory T cells (anergy T cells) and Foxp3-positive regulatory cells producing IL-10. Immunohistochemistry targeting IgG4, HLA-DR, CD80, CD86, and Foxp3 was performed using 54 cholangiocarcinoma specimens from 24 patients with gallbladder cancer, 22 patients with common bile duct cancer, and eight patients with cancer of the Papilla of Vater. Moreover, a molecular analysis of Foxp3 and IL-10 was performed using a cultured human cholangiocarcinoma cell line. Consequently, 43% of the cholangiocarcinomas were found to be abundant in IgG4. Those expressing HLA-DR but lacking costimulatory molecules (CD80 and CD86) and those expressing Foxp3 detected by an antibody recognizing the N terminus accounted for 54% and 39% of cases, respectively. Moreover, the number of IgG4-positive cells was larger in these cases than in other groups. In cultured cells, the presence of a splicing variant of Foxp3 messenger RNA and the expression of IL-10 were demonstrated. Conclusion: Extrahepatic cholangiocarcinoma is often accompanied by significant infiltration of IgG4-positive cells. Cholangiocarcinoma cells could play the role of nonprofessional APCs and Foxp3-positive regulatory cells, inducing IgG4 reactions via the production of IL-10 indirectly and directly, respectively. © 2012 American Association for the Study of Liver Diseases. 続きを見る

URL:

http://hdl.handle.net/2297/32121