LAUSR

Extracellular ATP is known to promote Th17 cell differentiation in the intestinal lamina propria by stimulating CD70 +CD11c low dendritic cells (DCs) via P2X receptors (P2XRs). Recent studies have also shown that Th17 cells enhance antitumor immunity by directly promoting proliferation of cytotoxic T lymphocytes (CTLs). These finding led us to test a P2XR agonist, αβ-methylene ATP (αβ-ATP), as a mucosal vaccine adjuvant to promote CTL responses through Th17 induction. We demonstrated that (1) CD70 +CD11c low DCs were present in the nasal lamina propria and expressed P2X1R, P2X2R and P2X4R; (2) CD70 +CD11c low DCs isolated from the nasal lamina propria enhanced Th17 cell differentiation of cocultured splenic CD4 + T cells upon stimulation with αβ-ATP; (3) mice intranasally immunized with ovalbumin (OVA) and αβ-ATP had increased OVA-specific Th17 cells and CTLs in the nasal lamina propria and regional lymph nodes; (4) mice intranasally immunized with OVA and αβ-ATP also had elevated resistance to E.G7-OVA tumor growth compared with those intranasally immunized with OVA alone; (5) suramin, a broad-range inhibitor of P2 receptors, suppressed the increases of OVA-specific Th17 cells and CTLs in mice intranasally immunized with OVA and αβ-ATP; (6) suramin also abrogated the enhanced antitumor immunity of mice intranasally immunized with OVA and αβ-ATP against E.G7-OVA. Collectively, αβ-ATP may be a promising mucosal adjuvant that promotes antigen-specific CTL responses via CD70 +CD11c low DC-mediated Th17 induction.