The receptor for advanced glycation end products (RAGE) affects T cell differentiation in OVA induced asthma

PLoS One. 2014 Apr 23;9(4):e95678. doi: 10.1371/journal.pone.0095678. eCollection 2014.

Abstract

The receptor for glycation end products (RAGE) has been previously implicated in shaping the adaptive immune response. RAGE is expressed in T cells after activation and constitutively in T cells from patients with diabetes. The effects of RAGE on adaptive immune responses are not clear: Previous reports show that RAGE blockade affects Th1 responses. To clarify the role of RAGE in adaptive immune responses and the mechanisms of its effects, we examined whether RAGE plays a role in T cell activation in a Th2 response involving ovalbumin (OVA)-induced asthma in mice. WT and RAGE deficient wild-type and OT-II mice, expressing a T cell receptor specific for OVA, were immunized intranasally with OVA. Lung cellular infiltration and T cell responses were analyzed by immunostaining, FACS, and multiplex bead analyses for cytokines. RAGE deficient mice showed reduced cellular infiltration in the bronchial alveolar lavage fluid and impaired T cell activation in the mediastinal lymph nodes when compared with WT mice. In addition, RAGE deficiency resulted in reduced OT-II T cell infiltration of the lung and impaired IFNγ and IL-5 production when compared with WT mice and reduced infiltration when transferred into WT hosts. When cultured under conditions favoring the differentiation of T cells subsets, RAGE deficient T cells showed reduced production of IFNγ but increased production of IL-17. Our data show a stimulatory role for RAGE in T activation in OVA-induced asthma. This role is largely mediated by the effects of RAGE on T cell proliferation and differentiation. These findings suggest that RAGE may play a regulatory role in T cell responses following immune activation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Asthma / chemically induced*
  • Asthma / genetics
  • Asthma / metabolism*
  • Cell Differentiation / genetics
  • Cell Differentiation / physiology
  • Female
  • Interferon-gamma / metabolism
  • Interleukin-17 / metabolism
  • Interleukin-5 / metabolism
  • Mice
  • Ovalbumin / toxicity*
  • Receptor for Advanced Glycation End Products
  • Receptors, Immunologic / genetics
  • Receptors, Immunologic / metabolism*
  • T-Lymphocyte Subsets / cytology
  • T-Lymphocyte Subsets / metabolism
  • Th2 Cells / cytology
  • Th2 Cells / metabolism

Substances

  • Interleukin-17
  • Interleukin-5
  • Receptor for Advanced Glycation End Products
  • Receptors, Immunologic
  • Interferon-gamma
  • Ovalbumin

Grant support

This work was support by JDRF grant 2004-808. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.