Details

Autor(en) / Beteiligte

• Tanner, S M
• Staley, E M
• Lorenz, R G

Titel

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

Ist Teil von

• Mucosal immunology, 2013-03, Vol.6 (2), p.309-323

Ort / Verlag

United States: Nature Publishing Group

Erscheinungsjahr

2013

Link zum Volltext

Quelle

MEDLINE

Beschreibungen/Notizen

• 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 Foxp3(+) 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 Foxp3(+)IL-17(+) cells. Instead, P-gp deficiency appears to restrict the development of induced Treg cells (iTregs), as fewer Foxp3(+) iTregs developed from naive FVB.mdr1a(-/-) T cells both upon transforming growth factor-β (TGF-β) treatment in vitro and after adoptive transfer into FVB.rag2(-/-) recipients. Rather, in vitro TGF-β treatment results in a IL-17(+)CD4(+) T cell. This failure of iTregs to develop explains the decrease in Foxp3(+) Tregs in the FVB.mdr1a(-/-) intestine, representing a need to investigate this novel disease mechanism in human inflammatory bowel disease patients with MDR1 polymorphisms.