Altered generation of induced regulatory T cells in the FVB.mdr1a(-/-) mouse model of colitis

作者：Tanner S M; Staley E M; Lorenz R G^*

来源：Mucosal Immunology, 2013, 6(2): 309-323.

DOI：10.1038/mi.2012.73

The FVB.mdr1a(-/-) mouse, lacking the small molecule pump P-glycoprotein (P-gp), is a commonly used model for the study of spontaneous T cell-mediated colitis. In addition, MDR1 polymorphisms and P-gp deficiency in humans have been linked to the development of ulcerative colitis. We now demonstrate that mice with P-gp deficiency have decreased levels of Foxp(3+) regulatory T cells (Tregs) in the intestinal lamina propria. This decrease is not due to either increased Treg apoptosis, altered Treg trafficking, or enhanced Treg plasticity to become Foxp(3+) IL-17(+) cells. Instead, P-gp deficiency appears to restrict the development of induced Treg cells (iTregs), as fewer Foxp(3+) iTregs developed from naive FVB.mdr1a(-/-) T cells both upon transforming growth factor- (TGF- )treatment in vitro and after adoptive transfer into FVB.mdr1a(-/-) recipients. Rather, in vitro TGF- treatment results in a IL-17(+) CD4(+) T cell. This failure of iTregs to develop explains the decrease in Foxp(3+) Tregs in the FVB.mdr1a(-/-) intestine, representing a need to investigate this novel disease mechanism in human inflammatory bowel disease patients with MDR1 polymorphisms.

• 出版日期2013-3