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P2X receptor agonist enhances tumor-specific CTL responses through CD70+ DC-mediated Th17 induction.
- Source :
-
International immunology [Int Immunol] 2021 Jan 01; Vol. 33 (1), pp. 49-55. - Publication Year :
- 2021
-
Abstract
- Extracellular ATP is known to promote Th17 cell differentiation in the intestinal lamina propria by stimulating CD70+CD11clow 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 (i) CD70+CD11clow DCs were present in the nasal lamina propria and expressed P2X1R, P2X2R and P2X4R; (ii) CD70+CD11clow DCs isolated from the nasal lamina propria enhanced Th17 cell differentiation of cocultured splenic CD4+ T cells upon stimulation with αβ-ATP; (iii) 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; (iv) 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; (v) 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; and (vi) 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+CD11clow DC-mediated Th17 induction.<br /> (© The Japanese Society for Immunology. 2020. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)
- Subjects :
- Adenosine Triphosphate metabolism
Animals
CD27 Ligand metabolism
Cell Differentiation immunology
Disease Models, Animal
Immunization
Intestinal Mucosa cytology
Intestinal Mucosa immunology
Lymphocyte Activation immunology
Melanoma, Experimental immunology
Mice
Mice, Inbred C57BL
Ovalbumin immunology
Purinergic P2X Receptor Antagonists pharmacology
Receptors, Purinergic P2X immunology
Suramin pharmacology
Th17 Cells immunology
Adjuvants, Vaccine therapeutic use
Dendritic Cells immunology
Melanoma, Experimental therapy
Ovalbumin administration & dosage
Purinergic P2X Receptor Agonists pharmacology
T-Lymphocytes, Cytotoxic immunology
Subjects
Details
- Language :
- English
- ISSN :
- 1460-2377
- Volume :
- 33
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- International immunology
- Publication Type :
- Academic Journal
- Accession number :
- 33027512
- Full Text :
- https://doi.org/10.1093/intimm/dxaa068