Oncotarget

Research Papers: Immunology:

Dysregulation of peritoneal cavity B1a cells and murine primary biliary cholangitis

Yan-Qing Yang, Wei Yang, Yuan Yao, Hong-Di Ma, Yin-Hu Wang, Liang Li, Qingfa Wu, M. Eric Gershwin and Zhe-Xiong Lian _

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Oncotarget. 2016; 7:26992-27006. https://doi.org/10.18632/oncotarget.8853

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Abstract

Yan-Qing Yang1, Wei Yang1, Yuan Yao1, Hong-Di Ma1, Yin-Hu Wang1, Liang Li1, Qingfa Wu2, M. Eric Gershwin3 and Zhe-Xiong Lian1,4

1 Liver Immunology Laboratory, Institute of Immunology and The CAS Key Laboratory of Innate Immunity and Chronic Disease, School of Life Sciences, University of Science and Technology of China, Hefei, China

2 The CAS Key Laboratory of Innate Immunity and Chronic Disease, School of Life Sciences, University of Science and Technology of China, Hefei, China

3 Division of Rheumatology, Allergy and Clinical Immunology, University of California at Davis School of Medicine, Davis, CA, United States of America

4 Innovation Center for Cell Signaling Network, Hefei National Laboratory for Physical Sciences at Microscale, Hefei, China

Correspondence to:

Zhe-Xiong Lian, email:

Hong-Di Ma, email:

Keywords: B1a cell, autoimmune cholangitis, dysregulation, Breg, peritoneal cavity, Immunology and Microbiology Section, Immune response, Immunity

Received: March 15, 2016 Accepted: April 13, 2016 Published: April 20, 2016

Abstract

Primary biliary cholangitis (PBC) is a chronic autoimmune liver disease with progressive cholestasis and liver fibrosis. Similar to human patients with PBC, p40-/-IL-2Rα-/- mice spontaneously develop severe autoimmune cholangitis. Although there has been considerable work on immune regulation and autoimmunity, there is a relative paucity of work directed at the functional implications of the key peritoneal cavity (PC) B cell subset, coined B1a cells in PBC. We used flow cytometry and high-resolution microarrays to study the qualitative and quantitative characteristics of B cells, particularly B1a cells, in the PC of p40-/-IL-2Rα-/- mice compared to controls. Importantly, B1a cell proliferation was markedly lower as the expression of Ki67 decreased. Meanwhile, the apoptosis level was much higher. These lead to a reduction of B1a cells in the PC of p40-/-IL-2Rα-/- mice compared to controls. In contrast, there was a dramatic increase of CD4+ and CD8+ T cells accompanied by elevated production of IFN-γ. In addition, we found a negative correlation between the frequency of B1a cells and the presence of autoreactive CD8+ T cells in both liver and PC of p40-/-IL-2Rα-/- mice. From a functional perspective, B cells from p40-/-IL-2Rα-/- mice downregulated IL-10 production and CTLA-4 expression, leading to loss of B cell regulatory function. We suggest that the dysfunction of B1a cells in the PC in this murine model of autoimmune cholangitis results in defective regulatory function. This highlights a new potential therapeutic target in PBC.


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