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Efficient T-cell priming and activation requires signaling through prostaglandin E2 (EP) receptors.
- Source :
- Immunology & Cell Biology; Jan2016, Vol. 94 Issue 1, p39-51, 13p
- Publication Year :
- 2016
-
Abstract
- Understanding the regulation of T-cell responses during inflammation and auto-immunity is fundamental for designing efficient therapeutic strategies against immune diseases. In this regard, prostaglandin E<subscript>2</subscript> (PGE<subscript>2</subscript>) is mostly considered a myeloid-derived immunosuppressive molecule. We describe for the first time that T cells secrete PGE<subscript>2</subscript> during T-cell receptor stimulation. In addition, we show that autocrine PGE<subscript>2</subscript> signaling through EP receptors is essential for optimal CD4<superscript>+</superscript> T-cell activation in vitro and in vivo, and for T helper 1 (Th1) and regulatory T cell differentiation. PGE<subscript>2</subscript> was found to provide additive co-stimulatory signaling through AKT activation. Intravital multiphoton microscopy showed that triggering EP receptors in T cells is also essential for the stability of T cell--dendritic cell (DC) interactions and Th-cell accumulation in draining lymph nodes (LNs) during inflammation. We further demonstrated that blocking EP receptors in T cells during the initial phase of collagen-induced arthritis in mice resulted in a reduction of clinical arthritis. This could be attributable to defective T-cell activation, accompanied by a decline in activated and interferon-γ-producing CD4<superscript>+</superscript> Th1 cells in draining LNs. In conclusion, we prove that T lymphocytes secret picomolar concentrations of PGE<subscript>2</subscript>, which in turn provide additive co-stimulatory signaling, enabling T cells to attain a favorable activation threshold. PGE<subscript>2</subscript> signaling in T cells is also required for maintaining long and stable interactions with DCs within LNs. Blockade of EP receptors in vivo impairs T-cell activation and development of T cell-mediated inflammatory responses. This may have implications in various pathophysiological settings. [ABSTRACT FROM AUTHOR]
- Subjects :
- T cells
DINOPROSTONE
CD4 antigen
IMMUNE response
DENDRITIC cells
Subjects
Details
- Language :
- English
- ISSN :
- 08189641
- Volume :
- 94
- Issue :
- 1
- Database :
- Complementary Index
- Journal :
- Immunology & Cell Biology
- Publication Type :
- Academic Journal
- Accession number :
- 130165038
- Full Text :
- https://doi.org/10.1038/icb.2015.62