B cells promote hepatic inflammation, biliary cyst formation, and salivary gland inflammation in the NOD.c3c4 model of autoimmune cholangitis

Yuki Moritoki, Masanobu Tsuda, Koichi Tsuneyama, Weici Zhang, Katsunori Yoshida, Zhe Xiong Lian, Guo Xiang Yang, William M. Ridgway, Linda S. Wicker, Aftab A. Ansari, M. Eric Gershwin

Research output: Contribution to journalArticle

17 Citations (Scopus)

Abstract

There are now several murine models of autoimmune cholangitis that have features both similar and distinct from human PBC. One such model, the NOD.c3c4 mouse, manifests portal cell infiltrates, anti-mitochondrial antibodies but also biliary cysts. The biliary cysts are not a component of PBC and not found in the other murine models. To address the immunopathology in these mice, we generated genetically B cell deficient Igμ -/- NOD.c3c4 mice and compared the immunopathology of these animals to control B cell sufficient NOD.c3c4 mice. B cell deficient mice demonstrated decreased number of non-B cells in the liver accompanied by reduced numbers of activated natural killer cells. The degree of granuloma formation and bile duct damage were comparable to NOD.c3c4 mice. In contrast, liver inflammation, biliary cyst formation and salivary gland inflammation was significantly attenuated in these B cell deficient mice. In conclusion, B cells play a critical role in promoting liver inflammation and also contribute to cyst formation as well as salivary gland pathology in autoimmune NOD.c3c4 mice, illustrating a critical role of B cells in modulating specific organ pathology and, in particular, in exacerbating both the biliary disease and the sialadenitis.

Original languageEnglish (US)
Pages (from-to)16-23
Number of pages8
JournalCellular Immunology
Volume268
Issue number1
DOIs
StatePublished - 2011

Fingerprint

Sialadenitis
Cholangitis
Cysts
B-Lymphocytes
Inflammation
Liver
Pathology
Bile Ducts
Salivary Glands
Granuloma
Natural Killer Cells
Anti-Idiotypic Antibodies

Keywords

  • Anti-mitochondrial antibodies
  • Autoimmune cholangitis
  • B cells
  • Mu deficient mice

ASJC Scopus subject areas

  • Immunology

Cite this

B cells promote hepatic inflammation, biliary cyst formation, and salivary gland inflammation in the NOD.c3c4 model of autoimmune cholangitis. / Moritoki, Yuki; Tsuda, Masanobu; Tsuneyama, Koichi; Zhang, Weici; Yoshida, Katsunori; Lian, Zhe Xiong; Yang, Guo Xiang; Ridgway, William M.; Wicker, Linda S.; Ansari, Aftab A.; Gershwin, M. Eric.

In: Cellular Immunology, Vol. 268, No. 1, 2011, p. 16-23.

Research output: Contribution to journalArticle

Moritoki, Yuki ; Tsuda, Masanobu ; Tsuneyama, Koichi ; Zhang, Weici ; Yoshida, Katsunori ; Lian, Zhe Xiong ; Yang, Guo Xiang ; Ridgway, William M. ; Wicker, Linda S. ; Ansari, Aftab A. ; Gershwin, M. Eric. / B cells promote hepatic inflammation, biliary cyst formation, and salivary gland inflammation in the NOD.c3c4 model of autoimmune cholangitis. In: Cellular Immunology. 2011 ; Vol. 268, No. 1. pp. 16-23.
@article{ffffa5dfb708439face509c4313913ab,
title = "B cells promote hepatic inflammation, biliary cyst formation, and salivary gland inflammation in the NOD.c3c4 model of autoimmune cholangitis",
abstract = "There are now several murine models of autoimmune cholangitis that have features both similar and distinct from human PBC. One such model, the NOD.c3c4 mouse, manifests portal cell infiltrates, anti-mitochondrial antibodies but also biliary cysts. The biliary cysts are not a component of PBC and not found in the other murine models. To address the immunopathology in these mice, we generated genetically B cell deficient Igμ -/- NOD.c3c4 mice and compared the immunopathology of these animals to control B cell sufficient NOD.c3c4 mice. B cell deficient mice demonstrated decreased number of non-B cells in the liver accompanied by reduced numbers of activated natural killer cells. The degree of granuloma formation and bile duct damage were comparable to NOD.c3c4 mice. In contrast, liver inflammation, biliary cyst formation and salivary gland inflammation was significantly attenuated in these B cell deficient mice. In conclusion, B cells play a critical role in promoting liver inflammation and also contribute to cyst formation as well as salivary gland pathology in autoimmune NOD.c3c4 mice, illustrating a critical role of B cells in modulating specific organ pathology and, in particular, in exacerbating both the biliary disease and the sialadenitis.",
keywords = "Anti-mitochondrial antibodies, Autoimmune cholangitis, B cells, Mu deficient mice",
author = "Yuki Moritoki and Masanobu Tsuda and Koichi Tsuneyama and Weici Zhang and Katsunori Yoshida and Lian, {Zhe Xiong} and Yang, {Guo Xiang} and Ridgway, {William M.} and Wicker, {Linda S.} and Ansari, {Aftab A.} and Gershwin, {M. Eric}",
year = "2011",
doi = "10.1016/j.cellimm.2011.01.005",
language = "English (US)",
volume = "268",
pages = "16--23",
journal = "Cellular Immunology",
issn = "0008-8749",
publisher = "Academic Press Inc.",
number = "1",

}

TY - JOUR

T1 - B cells promote hepatic inflammation, biliary cyst formation, and salivary gland inflammation in the NOD.c3c4 model of autoimmune cholangitis

AU - Moritoki, Yuki

AU - Tsuda, Masanobu

AU - Tsuneyama, Koichi

AU - Zhang, Weici

AU - Yoshida, Katsunori

AU - Lian, Zhe Xiong

AU - Yang, Guo Xiang

AU - Ridgway, William M.

AU - Wicker, Linda S.

AU - Ansari, Aftab A.

AU - Gershwin, M. Eric

PY - 2011

Y1 - 2011

N2 - There are now several murine models of autoimmune cholangitis that have features both similar and distinct from human PBC. One such model, the NOD.c3c4 mouse, manifests portal cell infiltrates, anti-mitochondrial antibodies but also biliary cysts. The biliary cysts are not a component of PBC and not found in the other murine models. To address the immunopathology in these mice, we generated genetically B cell deficient Igμ -/- NOD.c3c4 mice and compared the immunopathology of these animals to control B cell sufficient NOD.c3c4 mice. B cell deficient mice demonstrated decreased number of non-B cells in the liver accompanied by reduced numbers of activated natural killer cells. The degree of granuloma formation and bile duct damage were comparable to NOD.c3c4 mice. In contrast, liver inflammation, biliary cyst formation and salivary gland inflammation was significantly attenuated in these B cell deficient mice. In conclusion, B cells play a critical role in promoting liver inflammation and also contribute to cyst formation as well as salivary gland pathology in autoimmune NOD.c3c4 mice, illustrating a critical role of B cells in modulating specific organ pathology and, in particular, in exacerbating both the biliary disease and the sialadenitis.

AB - There are now several murine models of autoimmune cholangitis that have features both similar and distinct from human PBC. One such model, the NOD.c3c4 mouse, manifests portal cell infiltrates, anti-mitochondrial antibodies but also biliary cysts. The biliary cysts are not a component of PBC and not found in the other murine models. To address the immunopathology in these mice, we generated genetically B cell deficient Igμ -/- NOD.c3c4 mice and compared the immunopathology of these animals to control B cell sufficient NOD.c3c4 mice. B cell deficient mice demonstrated decreased number of non-B cells in the liver accompanied by reduced numbers of activated natural killer cells. The degree of granuloma formation and bile duct damage were comparable to NOD.c3c4 mice. In contrast, liver inflammation, biliary cyst formation and salivary gland inflammation was significantly attenuated in these B cell deficient mice. In conclusion, B cells play a critical role in promoting liver inflammation and also contribute to cyst formation as well as salivary gland pathology in autoimmune NOD.c3c4 mice, illustrating a critical role of B cells in modulating specific organ pathology and, in particular, in exacerbating both the biliary disease and the sialadenitis.

KW - Anti-mitochondrial antibodies

KW - Autoimmune cholangitis

KW - B cells

KW - Mu deficient mice

UR - http://www.scopus.com/inward/record.url?scp=79952484948&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=79952484948&partnerID=8YFLogxK

U2 - 10.1016/j.cellimm.2011.01.005

DO - 10.1016/j.cellimm.2011.01.005

M3 - Article

VL - 268

SP - 16

EP - 23

JO - Cellular Immunology

JF - Cellular Immunology

SN - 0008-8749

IS - 1

ER -