| First Author | Yang YQ | Year | 2016 |
| Journal | Oncotarget | Volume | 7 |
| Issue | 19 | Pages | 26992-7006 |
| PubMed ID | 27105495 | Mgi Jnum | J:336465 |
| Mgi Id | MGI:6832127 | Doi | 10.18632/oncotarget.8853 |
| Citation | Yang YQ, et al. (2016) Dysregulation of peritoneal cavity B1a cells and murine primary biliary cholangitis. Oncotarget 7(19):26992-7006 |
| abstractText | Primary biliary cholangitis (PBC) is a chronic autoimmune liver disease with progressive cholestasis and liver fibrosis. Similar to human patients with PBC, p40-/-IL-2Ralpha-/- 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-2Ralpha-/- 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-2Ralpha-/- mice compared to controls. In contrast, there was a dramatic increase of CD4+ and CD8+ T cells accompanied by elevated production of IFN-gamma. 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-2Ralpha-/- mice. From a functional perspective, B cells from p40-/-IL-2Ralpha-/- 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. |
