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The Roles of Type 2 Cytotoxic T Cells in Inflammation, Tissue Remodeling, and Prostaglandin (PG) D₂ Production Are Attenuated by PGD₂ Receptor 2 Antagonism.

ABSTRACT: 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.

SUBMITTER: Chen W

PROVIDER: S-EPMC7610864 | biostudies-literature | 2021 Jun

REPOSITORIES: biostudies-literature

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The Roles of Type 2 Cytotoxic T Cells in Inflammation, Tissue Remodeling, and Prostaglandin (PG) D2 Production Are Attenuated by PGD2 Receptor 2 Antagonism.

Chen Wentao W Luo Jian J Ye Yuan Y Hoyle Ryan R Liu Wei W Borst Rowie R Kazani Shamsah S Shikatani Eric A EA Erpenbeck Veit J VJ Pavord Ian D ID Klenerman Paul P Sandham David A DA Xue Luzheng L

Journal of immunology (Baltimore, Md. : 1950) 20210519 11

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 ...[more]

PMID: 34011519

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The Roles of Type 2 Cytotoxic T Cells in Inflammation, Tissue Remodeling, and Prostaglandin (PG) D&lt;sub&gt;2&lt;/sub&gt; Production Are Attenuated by PGD&lt;sub&gt;2&lt;/sub&gt; Receptor 2 Antagonism.

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OmicsDI is part of the ELIXIR infrastructure

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The Roles of Type 2 Cytotoxic T Cells in Inflammation, Tissue Remodeling, and Prostaglandin (PG) D₂ Production Are Attenuated by PGD₂ Receptor 2 Antagonism.

The Roles of Type 2 Cytotoxic T Cells in Inflammation, Tissue Remodeling, and Prostaglandin (PG) D<sub>2</sub> Production Are Attenuated by PGD<sub>2</sub> Receptor 2 Antagonism.