The roles of type 2 cytotoxic T cells in inflammation, tissue remodeling, and prostaglandin (PG) D2 production are attenuated by PGD2 receptor 2 antagonism

Journal article

Human type 2 cytotoxic T (Tc2) cells are enriched in severe eosinophilic asthma and can contribute to airway eosinophilia. PGD₂ and its receptor PGD₂ receptor 2 (DP2) play important roles in Tc2 cell activation, including migration, cytokine production, and survival. In this study, we revealed novel, to our knowledge, functions of the PGD₂/DP2 axis in Tc2 cells to induce tissue-remodeling effects and IgE-independent PGD₂ autocrine production. PGD₂ upregulated the expression of tissue-remodeling genes in Tc2 cells that enhanced the fibroblast proliferation and protein production required for tissue repair and myofibroblast differentiation. PGD₂ stimulated Tc2 cells to produce PGD₂ using the routine PGD₂ synthesis pathway, which also contributed to TCR-dependent PGD₂ production in Tc2 cells. Using fevipiprant, a specific DP2 antagonist, we demonstrated that competitive inhibition of DP2 not only completely blocked the cell migration, adhesion, proinflammatory cytokine production, and survival of Tc2 cells triggered by PGD₂ but also attenuated the tissue-remodeling effects and autocrine/paracrine PGD₂ production in Tc2 induced by PGD₂ and other stimulators. These findings further confirmed the anti-inflammatory effect of fevipiprant and provided a better understanding of the role of Tc2 cells in the pathogenesis of asthma.

Authors: Chen, W; Luo, J; Ye, Y; Hoyle, R; Liu, W

• Publication status: Published
• Peer review status: Peer reviewed
• Publisher: American Association of Immunologists
• Journal: Journal of Immunology
• Volume: 206
• Issue: 11
• Pages: 2714-2724
• Publication date: 2021-06-01
• Acceptance date: 2021-03-20
• DOI: 10.4049/jimmunol.2001245
• EISSN: 1550-6606
• ISSN: 0022-1767
• Pmid: 34011519
• Language: English
• Keywords: prostaglandin receptors; inflammation; FFR; indoleacetic acids; cultured cells; prostaglandin D2; coculture techniques; immunologic receptors; pyridines; cytotoxic T-lymphocytes