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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
New York: Nature Publishing Group US
Erscheinungsjahr
2013
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.