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

Academic Article

Abstract

  • 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. © 2013 Society for Mucosal Immunology.
  • Published In

  • Mucosal Immunology  Journal
  • Digital Object Identifier (doi)

    Author List

  • Tanner SM; Staley EM; Lorenz RG
  • Start Page

  • 309
  • End Page

  • 323
  • Volume

  • 6
  • Issue

  • 2