The receptor for advanced glycation end products (RAGE) affects T cell differentiation in OVA induced asthma.
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.
Research Institute, Islet Biology, Winthrop University Hospital, Mineola, New York, United States of America; and Stony Brook University School of Medicine, Stony Brook, New York, United States of America.
Eitan M
EM
Akirav
Department of Immunobiology, Yale University School of Medicine, New Haven, Connecticut, United States of America.
Octavian
O
Henegariu
Department of Immunobiology, Yale University School of Medicine, New Haven, Connecticut, United States of America.
Paula
P
Preston-Hurlburt
Department of Medicine, New York University School of Medicine, New York, New York, United States of America.
Ann Marie
AM
Schmidt
Department of Medicine, Columbia University, New York, New York, United States of America.
Raphael
R
Clynes
Department of Immunobiology, Yale University School of Medicine, New Haven, Connecticut, United States of America; Internal Medicine, Yale University School of Medicine, New Haven, Connecticut, United States of America.
Kevan C
KC
Herold
D000818:Animals; D001249:Asthma / Q000139:chemically induced* / Q000235:genetics / Q000378:metabolism*; D002454:Cell Differentiation / Q000235:genetics / Q000502:physiology; D005260:Female; D007371:Interferon-gamma / Q000378:metabolism; D020381:Interleukin-17 / Q000378:metabolism; D015848:Interleukin-5 / Q000378:metabolism; D051379:Mice; D010047:Ovalbumin / Q000633:toxicity*; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic / Q000235:genetics / Q000378:metabolism*; D016176:T-Lymphocyte Subsets / Q000166:cytology / Q000378:metabolism; D018418:Th2 Cells / Q000166:cytology / Q000378:metabolism
D020381:Interleukin-17; D015848:Interleukin-5; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic; D007371:Interferon-gamma; D010047:Ovalbumin