Title: Receptor for advanced glycation end products is required for normal T cell activation and development of T cell induced lung inflammation (36.10)
Abstract:Abstract We have shown that the receptor for advanced glycation endproducts (RAGE) is required for normal T cell activation and differentiation into Th1 cells, since RAGE-/- T cells show reduced proli...Abstract We have shown that the receptor for advanced glycation endproducts (RAGE) is required for normal T cell activation and differentiation into Th1 cells, since RAGE-/- T cells show reduced proliferation and IFNγ expression after activation with alloantigens. Here, we examined T cell activation in RAGE-/- and OT-II.RAGE-/- mice in a model of T cell induced asthma. Intranasal OVA challenge of RAGE-/- mice resulted in reduced T cell activation as measured by increased CD62L expression, decreased CD69 expression, and reduced IL5 production. Cellular infiltrates in the lungs of OVA immunized RAGE-/- mice were reduced when compared with WT mice. Intranasal OVA challenge of OT-II mice induced a robust T cell infiltration of the lung, which was reduced in OT-II.RAGE-/- mice. Moreover, cells from mediastinal lymph nodes of OT-II.RAGE-/- mice showed reduced IL2, IL5, IL10, IL12, and IFN? production. Interestingly, purified RAGE-/- T cells showed lower basal levels of Ca2+ flux when compared with WT cells. These levels were not corrected in response to αCD3 stimulation. Reduced Ca2+ flux was associated with reduced expression of the transcription factor T-bet but with no change in GATA-3 expression in RAGE-/- T cells. In summary, these results reveal an unexpected defect in Ca2+ flux of RAGE deficient T cells under basal and activated conditions and reduced T cell activation in OVA-induced asthma, suggesting a novel role for RAGE in T cell signaling.Read More
Publication Year: 2009
Publication Date: 2009-04-01
Language: en
Type: article
Indexed In: ['crossref']
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