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, Zhe Xiong Lian

Research output: Contribution to journalArticle

8 Scopus citations

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-2Ra-/- 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 highresolution microarrays to study the qualitative and quantitative characteristics of B cells, particularly B1a cells, in the PC of p40-/-IL-2Ra-/- 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-2Ra-/- 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-2Ra-/- mice. From a functional perspective, B cells from p40-/-IL-2Ra-/- 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.

Original languageEnglish (US)
Pages (from-to)26992-27006
Number of pages15
JournalOncotarget
Volume7
Issue number19
DOIs
StatePublished - May 10 2016

Keywords

  • Autoimmune cholangitis
  • B1a cell
  • Breg
  • Dysregulation
  • Immune response
  • Immunity
  • Immunology and microbiology section
  • Peritoneal cavity

ASJC Scopus subject areas

  • Oncology

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    Yang, Y. Q., Yang, W., Yao, Y., Ma, H. D., Wang, Y. H., Li, L., Wu, Q., Gershwin, M. E., & Lian, Z. X. (2016). Dysregulation of peritoneal cavity B1a cells and murine primary biliary cholangitis. Oncotarget, 7(19), 26992-27006. https://doi.org/10.18632/oncotarget.8853