Receptor for Advanced Glycation End Products Expression on T Cells Contributes to Antigen-Specific Cellular Expansion In Vivo

Abstract

Receptor for advanced glycation end products (RAGE) is an activation receptor triggered by inflammatory S100/calgranulins and high mobility group box-1 ligands. We have investigated the importance of RAGE on Ag priming of T cells in murine models in vivo. RAGE is inducibly up-regulated during T cell activation. Transfer of RAGE-deficient OT II T cells into OVA-immunized hosts resulted in reduced proliferative responses that were further diminished in RAGE-deficient recipients. Examination of RAGE-deficient dendritic cells did not reveal functional impairment in Ag presentation, maturation, or migratory capacities. However, RAGE-deficient T cells showed markedly impaired proliferative responses in vitro to nominal and alloantigens, in parallel with decreased production of IFN-γ and IL-2. These data indicate that RAGE expressed on T cells is required for efficient priming of T cells and elucidate critical roles for RAGE engagement during cognate dendritic cell-T cell interactions.

RAGE is a nucleic acid receptor that promotes inflammatory responses to DNA

“…Although RAGE has been reported to be expressed on several types of mammalian leukocytes (Brett et al, 1993;Dumitriu et al, 2007;Moser et al, 2007), RAGE is most highly expressed in mammalian lung epithelia (Demling et al, 2006;Buckley and Ehrhardt, 2010; this study). We therefore hypothesized that RAGE might participate in immune recognition of DNA in the airways.…”

Multiple levels of regulation determine the role of the receptor for AGE (RAGE) as common soil in inflammation, immune responses and diabetes mellitus and its complications

“…Furthermore, clonal populations of Rage −/− mice-derived T cells adoptively Monocytes and macrophages seem to be central to the initiation and propagation of RAGE-dependent inflammation transferred into wild-type recipients showed reduced responses [82]. Syngeneic islet graft and islet allograft rejection were reduced in diabetic mice treated with small molecule RAGE inhibitors and in diabetic Rage −/− mice [80], suggesting a close link between RAGE and the pathogenesis of type 1 diabetes [15].…”

Longistatin in tick saliva blocks advanced glycation end-product receptor activation

“…However, its expression increases at the site of inflammation or where its ligands are accumulated. RAGE/ligand interaction initiates sustained cellular activation through receptor-dependent signaling involving the transcription factor NF-κB and proinflammatory cytokine production, leading to leukocyte recruitment and subsequent initiation of inflammation in different pathological settings (7,15,16). Owing to severe tissue damage, it is quite reasonable that tick biting, at least at the site of attachment, causes the release of DAMPs from the devitalized tissues and is most likely to be responsible for igniting inflammatory responses, which tend to prevent the damaging activities of ticks.…”