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The PGI2 Analog Cicaprost Inhibits IL-33-Induced Th2 Responses, IL-2 Production, and CD25 Expression in Mouse CD4+ T Cells.


ABSTRACT: IL-33 has pleiotropic functions in immune responses and promotes the development of allergic diseases and asthma. IL-33 induces Th2 differentiation and enhances type 2 cytokine production by CD4+ T cells. However, the regulation of IL-33-driven type 2 cytokine responses is not fully defined. In this study, we investigated the effect of PGI2, a lipid mediator formed in the cyclooxygenase pathway of arachidonic acid metabolism, on naive CD4+ T cell activation, proliferation, and differentiation by IL-33. Using wild-type and PGI2 receptor (IP) knockout mice, we found that the PGI2 analog cicaprost dose-dependently inhibited IL-33-driven IL-4, IL-5, and IL-13 production by CD4+ T cells in an IP-specific manner. In addition, cicaprost inhibited IL-33-driven IL-2 production and CD25 expression by CD4+ T cells. Furthermore, IP knockout mice had increased IL-5 and IL-13 responses of CD4+ T cells to Alternaria sensitization and challenge in mouse lungs. Because IL-33 is critical for Alternaria-induced type 2 responses, these data suggest that PGI2 not only inhibits IL-33-stimulated CD4+ Th2 cell responses in vitro but also suppresses IL-33-induced Th2 responses caused by protease-containing allergens in vivo.

SUBMITTER: Zhou W 

PROVIDER: S-EPMC6162094 | biostudies-literature | 2018 Oct

REPOSITORIES: biostudies-literature

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The PGI<sub>2</sub> Analog Cicaprost Inhibits IL-33-Induced Th2 Responses, IL-2 Production, and CD25 Expression in Mouse CD4<sup>+</sup> T Cells.

Zhou Weisong W   Zhang Jian J   Toki Shinji S   Goleniewska Kasia K   Johnson Marc O MO   Bloodworth Melissa H MH   Newcomb Dawn C DC   Peebles R Stokes RS  

Journal of immunology (Baltimore, Md. : 1950) 20180820 7


IL-33 has pleiotropic functions in immune responses and promotes the development of allergic diseases and asthma. IL-33 induces Th2 differentiation and enhances type 2 cytokine production by CD4<sup>+</sup> T cells. However, the regulation of IL-33-driven type 2 cytokine responses is not fully defined. In this study, we investigated the effect of PGI<sub>2</sub>, a lipid mediator formed in the cyclooxygenase pathway of arachidonic acid metabolism, on naive CD4<sup>+</sup> T cell activation, prol  ...[more]

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