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Characterization of Immune Cells and Proinflammatory Mediators in the Pulmonary Environment
Published on: June 24, 2020
COX-2-Derived PGE2 Modulates IL-17 Production by γδ T Cells During Allergic Lung Inflammation
Chiguang Feng1, Hong Li1, Daniel Menendez1
1Immunity, Inflammation, and Disease Laboratory, Durham, North Carolina, USA.
Summary
Cyclooxygenase-2 (COX-2) derived prostaglandin E2 (PGE2) promotes IL-17A production in gamma delta (γδ) T cells, crucial for allergic lung inflammation. This occurs via EP2 and EP4 receptors, highlighting a new therapeutic target.
Area of Science:
- Immunology
- Inflammation Biology
- T cell Biology
Background:
- Cyclooxygenase-2 (COX-2) derived prostaglandins (PGs) influence T helper cell differentiation in allergic lung inflammation.
- Interleukin-17 (IL-17) is a key cytokine in allergic immunopathology, primarily produced by γδ T cells, not conventional αβ T cells.
- The role of COX-2 derived PGs in regulating γδ T cells during allergic lung inflammation is not well understood.
Purpose of the Study:
- To investigate the regulatory role of COX-2 derived PGs on γδ T cells in the context of allergic lung inflammation.
- To determine the specific prostaglandin involved and its mechanism of action on γδ T cell IL-17A production.
Main Methods:
- Utilized both in vivo and in vitro assays using COX-2 knockout (COX-2-/-) and wild-type (COX-2+/+) mice.
- Analyzed IL-17A production in bronchoalveolar lavage fluid (BALF) and isolated γδ T cells.
- Performed single-cell RNA sequencing (scRNA-seq) and quantitative PCR (qPCR) to identify prostaglandin E2 (PGE2) receptors on γδ T cells.
- Investigated the effect of PGE2 and its receptor antagonists (EP2, EP4) on IL-17A production.
Main Results:
- COX-2 disruption reduced IL-17A production in BALF during ovalbumin (OVA)-induced allergic lung inflammation without changing the number of IL-17A-producing γδ T cells.
- Isolated γδ T cells from COX-2-/- mice produced significantly less IL-17A upon stimulation with IL-1β + IL-23 compared to wild-type.
- PGE2 was identified as the primary PG that enhanced IL-1β + IL-23-induced IL-17A production by γδ T cells.
- γδ T cells express EP2 and EP4 receptors for PGE2, and antagonists for these receptors attenuated PGE2-mediated IL-17A production.
Conclusions:
- COX-2 derived PGE2 plays a significant role in enhancing IL-17A production by γδ T cells during allergic lung inflammation.
- This enhancement is mediated through the EP2 and EP4 receptors on γδ T cells.
- These findings reveal a novel mechanism by which COX-2 influences allergic lung inflammation and suggest potential therapeutic targets.
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