Liver-targeted and peripheral blood alterations of regulatory T cells in primary biliary cirrhosis

Ruth Y. Lan, Chunmei Cheng, Zhe Xiong Lian, Koichi Tsuneyama, Guo Xiang Yang, Yuki Moritoki, Ya Hui Chuang, Takafumi Nakamura, Shigeru Saito, Shinji Shimoda, Atsushi Tanaka, Christopher L. Bowlus, Yasuo Takano, Aftab A. Ansari, Ross L. Coppel, M. Eric Gershwin

研究成果: ジャーナルへの寄稿記事

227 引用 (Scopus)

抄録

CD4+CD25high regulatory T cells (Tregs) play a critical role in self-tolerance, as seen in murine autoimmunity. Studies on Tregs in human autoimmunity have focused primarily on peripheral blood samples. A study targeting diseased tissue should identify direct relationships between Tregs and autoimmunity. Peripheral blood samples were collected from 91 patients with primary biliary cirrhosis (PBC), 28 immediate relatives, and 41 healthy controls, and Treg frequencies were determined as a percentage of CD4+CD25high T cells in CD4+TCR-αβ+ T cells. A tissue-targeted determination of frequency and distribution of FoxP3+ Tregs was also performed on 90 different liver tissue specimens exhibiting PBC (n = 52), chronic hepatitis C (CHC) (n = 30), and autoimmune hepatitis (AIH) (n = 8). Treg suppression studies were performed on 50 PBC patients and 27 controls. Patients with PBC demonstrated a relative reduction of Tregs compared with controls (P < .0002). Interestingly, a deficiency in CD4+CD25+ Tregs was also found in the daughters and sisters of PBC patients compared with controls (P < .0007). However, functional studies did not reveal a global PBC Treg defect. The level of FoxP3-expressing Tregs was markedly lower in affected PBC portal tracts compared with CHC and AIH (P < .001). In addition, the CD8+ T cell/FoxP3+ Treg ratio was significantly higher in livers of late-stage PBC compared with those of CHC (P < .001) and early-stage AIH (P < .001). In conclusion, these data provide support for a genetic modulation of Treg frequency and illustrate the role Tregs play in the loss of tolerance in PBC.

元の言語英語
ページ(範囲)729-737
ページ数9
ジャーナルHepatology
43
発行部数4
DOI
出版物ステータス出版済み - 4 1 2006

Fingerprint

Biliary Liver Cirrhosis
Regulatory T-Lymphocytes
Liver
Autoimmune Hepatitis
Chronic Hepatitis C
Autoimmunity
T-Lymphocytes
Self Tolerance
Nuclear Family
Siblings

All Science Journal Classification (ASJC) codes

  • Hepatology

これを引用

Lan, R. Y., Cheng, C., Lian, Z. X., Tsuneyama, K., Yang, G. X., Moritoki, Y., ... Gershwin, M. E. (2006). Liver-targeted and peripheral blood alterations of regulatory T cells in primary biliary cirrhosis. Hepatology, 43(4), 729-737. https://doi.org/10.1002/hep.21123

Liver-targeted and peripheral blood alterations of regulatory T cells in primary biliary cirrhosis. / Lan, Ruth Y.; Cheng, Chunmei; Lian, Zhe Xiong; Tsuneyama, Koichi; Yang, Guo Xiang; Moritoki, Yuki; Chuang, Ya Hui; Nakamura, Takafumi; Saito, Shigeru; Shimoda, Shinji; Tanaka, Atsushi; Bowlus, Christopher L.; Takano, Yasuo; Ansari, Aftab A.; Coppel, Ross L.; Gershwin, M. Eric.

:: Hepatology, 巻 43, 番号 4, 01.04.2006, p. 729-737.

研究成果: ジャーナルへの寄稿記事

Lan, RY, Cheng, C, Lian, ZX, Tsuneyama, K, Yang, GX, Moritoki, Y, Chuang, YH, Nakamura, T, Saito, S, Shimoda, S, Tanaka, A, Bowlus, CL, Takano, Y, Ansari, AA, Coppel, RL & Gershwin, ME 2006, 'Liver-targeted and peripheral blood alterations of regulatory T cells in primary biliary cirrhosis', Hepatology, 巻. 43, 番号 4, pp. 729-737. https://doi.org/10.1002/hep.21123
Lan RY, Cheng C, Lian ZX, Tsuneyama K, Yang GX, Moritoki Y その他. Liver-targeted and peripheral blood alterations of regulatory T cells in primary biliary cirrhosis. Hepatology. 2006 4 1;43(4):729-737. https://doi.org/10.1002/hep.21123
Lan, Ruth Y. ; Cheng, Chunmei ; Lian, Zhe Xiong ; Tsuneyama, Koichi ; Yang, Guo Xiang ; Moritoki, Yuki ; Chuang, Ya Hui ; Nakamura, Takafumi ; Saito, Shigeru ; Shimoda, Shinji ; Tanaka, Atsushi ; Bowlus, Christopher L. ; Takano, Yasuo ; Ansari, Aftab A. ; Coppel, Ross L. ; Gershwin, M. Eric. / Liver-targeted and peripheral blood alterations of regulatory T cells in primary biliary cirrhosis. :: Hepatology. 2006 ; 巻 43, 番号 4. pp. 729-737.
@article{ace2045522e74acba3c3669fedbdf060,
title = "Liver-targeted and peripheral blood alterations of regulatory T cells in primary biliary cirrhosis",
abstract = "CD4+CD25high regulatory T cells (Tregs) play a critical role in self-tolerance, as seen in murine autoimmunity. Studies on Tregs in human autoimmunity have focused primarily on peripheral blood samples. A study targeting diseased tissue should identify direct relationships between Tregs and autoimmunity. Peripheral blood samples were collected from 91 patients with primary biliary cirrhosis (PBC), 28 immediate relatives, and 41 healthy controls, and Treg frequencies were determined as a percentage of CD4+CD25high T cells in CD4+TCR-αβ+ T cells. A tissue-targeted determination of frequency and distribution of FoxP3+ Tregs was also performed on 90 different liver tissue specimens exhibiting PBC (n = 52), chronic hepatitis C (CHC) (n = 30), and autoimmune hepatitis (AIH) (n = 8). Treg suppression studies were performed on 50 PBC patients and 27 controls. Patients with PBC demonstrated a relative reduction of Tregs compared with controls (P < .0002). Interestingly, a deficiency in CD4+CD25+ Tregs was also found in the daughters and sisters of PBC patients compared with controls (P < .0007). However, functional studies did not reveal a global PBC Treg defect. The level of FoxP3-expressing Tregs was markedly lower in affected PBC portal tracts compared with CHC and AIH (P < .001). In addition, the CD8+ T cell/FoxP3+ Treg ratio was significantly higher in livers of late-stage PBC compared with those of CHC (P < .001) and early-stage AIH (P < .001). In conclusion, these data provide support for a genetic modulation of Treg frequency and illustrate the role Tregs play in the loss of tolerance in PBC.",
author = "Lan, {Ruth Y.} and Chunmei Cheng and Lian, {Zhe Xiong} and Koichi Tsuneyama and Yang, {Guo Xiang} and Yuki Moritoki and Chuang, {Ya Hui} and Takafumi Nakamura and Shigeru Saito and Shinji Shimoda and Atsushi Tanaka and Bowlus, {Christopher L.} and Yasuo Takano and Ansari, {Aftab A.} and Coppel, {Ross L.} and Gershwin, {M. Eric}",
year = "2006",
month = "4",
day = "1",
doi = "10.1002/hep.21123",
language = "English",
volume = "43",
pages = "729--737",
journal = "Hepatology",
issn = "0270-9139",
publisher = "John Wiley and Sons Ltd",
number = "4",

}

TY - JOUR

T1 - Liver-targeted and peripheral blood alterations of regulatory T cells in primary biliary cirrhosis

AU - Lan, Ruth Y.

AU - Cheng, Chunmei

AU - Lian, Zhe Xiong

AU - Tsuneyama, Koichi

AU - Yang, Guo Xiang

AU - Moritoki, Yuki

AU - Chuang, Ya Hui

AU - Nakamura, Takafumi

AU - Saito, Shigeru

AU - Shimoda, Shinji

AU - Tanaka, Atsushi

AU - Bowlus, Christopher L.

AU - Takano, Yasuo

AU - Ansari, Aftab A.

AU - Coppel, Ross L.

AU - Gershwin, M. Eric

PY - 2006/4/1

Y1 - 2006/4/1

N2 - CD4+CD25high regulatory T cells (Tregs) play a critical role in self-tolerance, as seen in murine autoimmunity. Studies on Tregs in human autoimmunity have focused primarily on peripheral blood samples. A study targeting diseased tissue should identify direct relationships between Tregs and autoimmunity. Peripheral blood samples were collected from 91 patients with primary biliary cirrhosis (PBC), 28 immediate relatives, and 41 healthy controls, and Treg frequencies were determined as a percentage of CD4+CD25high T cells in CD4+TCR-αβ+ T cells. A tissue-targeted determination of frequency and distribution of FoxP3+ Tregs was also performed on 90 different liver tissue specimens exhibiting PBC (n = 52), chronic hepatitis C (CHC) (n = 30), and autoimmune hepatitis (AIH) (n = 8). Treg suppression studies were performed on 50 PBC patients and 27 controls. Patients with PBC demonstrated a relative reduction of Tregs compared with controls (P < .0002). Interestingly, a deficiency in CD4+CD25+ Tregs was also found in the daughters and sisters of PBC patients compared with controls (P < .0007). However, functional studies did not reveal a global PBC Treg defect. The level of FoxP3-expressing Tregs was markedly lower in affected PBC portal tracts compared with CHC and AIH (P < .001). In addition, the CD8+ T cell/FoxP3+ Treg ratio was significantly higher in livers of late-stage PBC compared with those of CHC (P < .001) and early-stage AIH (P < .001). In conclusion, these data provide support for a genetic modulation of Treg frequency and illustrate the role Tregs play in the loss of tolerance in PBC.

AB - CD4+CD25high regulatory T cells (Tregs) play a critical role in self-tolerance, as seen in murine autoimmunity. Studies on Tregs in human autoimmunity have focused primarily on peripheral blood samples. A study targeting diseased tissue should identify direct relationships between Tregs and autoimmunity. Peripheral blood samples were collected from 91 patients with primary biliary cirrhosis (PBC), 28 immediate relatives, and 41 healthy controls, and Treg frequencies were determined as a percentage of CD4+CD25high T cells in CD4+TCR-αβ+ T cells. A tissue-targeted determination of frequency and distribution of FoxP3+ Tregs was also performed on 90 different liver tissue specimens exhibiting PBC (n = 52), chronic hepatitis C (CHC) (n = 30), and autoimmune hepatitis (AIH) (n = 8). Treg suppression studies were performed on 50 PBC patients and 27 controls. Patients with PBC demonstrated a relative reduction of Tregs compared with controls (P < .0002). Interestingly, a deficiency in CD4+CD25+ Tregs was also found in the daughters and sisters of PBC patients compared with controls (P < .0007). However, functional studies did not reveal a global PBC Treg defect. The level of FoxP3-expressing Tregs was markedly lower in affected PBC portal tracts compared with CHC and AIH (P < .001). In addition, the CD8+ T cell/FoxP3+ Treg ratio was significantly higher in livers of late-stage PBC compared with those of CHC (P < .001) and early-stage AIH (P < .001). In conclusion, these data provide support for a genetic modulation of Treg frequency and illustrate the role Tregs play in the loss of tolerance in PBC.

UR - http://www.scopus.com/inward/record.url?scp=33646000803&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=33646000803&partnerID=8YFLogxK

U2 - 10.1002/hep.21123

DO - 10.1002/hep.21123

M3 - Article

C2 - 16557534

AN - SCOPUS:33646000803

VL - 43

SP - 729

EP - 737

JO - Hepatology

JF - Hepatology

SN - 0270-9139

IS - 4

ER -