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.