Efficient T-cell priming and activation requires signaling through prostaglandin E2 (EP) receptors


Autoria(s): Sreeramkumar, Vinatha; Hons, Miroslav; Punzón, Carmen; Stein, Jens Volker; Sancho, David; Fresno, Manuel; Cuesta, Natalia
Data(s)

01/01/2016

Resumo

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 E2 (PGE2) is mostly considered a myeloid-derived immunosuppressive molecule. We describe for the first time that T cells secrete PGE2 during T-cell receptor stimulation. In addition, we show that autocrine PGE2 signaling through EP receptors is essential for optimal CD4(+) T-cell activation in vitro and in vivo, and for T helper 1 (Th1) and regulatory T cell differentiation. PGE2 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(+) Th1 cells in draining LNs. In conclusion, we prove that T lymphocytes secret picomolar concentrations of PGE2, which in turn provide additive co-stimulatory signaling, enabling T cells to attain a favorable activation threshold. PGE2 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.

Formato

application/pdf

Identificador

http://boris.unibe.ch/77345/1/icb201562a.pdf

Sreeramkumar, Vinatha; Hons, Miroslav; Punzón, Carmen; Stein, Jens Volker; Sancho, David; Fresno, Manuel; Cuesta, Natalia (2016). Efficient T-cell priming and activation requires signaling through prostaglandin E2 (EP) receptors. Immunology and cell biology, 94(1), pp. 39-51. Nature Publishing Group 10.1038/icb.2015.62 <http://dx.doi.org/10.1038/icb.2015.62>

doi:10.7892/boris.77345

info:doi:10.1038/icb.2015.62

info:pmid:26051593

urn:issn:0818-9641

Idioma(s)

eng

Publicador

Nature Publishing Group

Relação

http://boris.unibe.ch/77345/

Direitos

info:eu-repo/semantics/restrictedAccess

Fonte

Sreeramkumar, Vinatha; Hons, Miroslav; Punzón, Carmen; Stein, Jens Volker; Sancho, David; Fresno, Manuel; Cuesta, Natalia (2016). Efficient T-cell priming and activation requires signaling through prostaglandin E2 (EP) receptors. Immunology and cell biology, 94(1), pp. 39-51. Nature Publishing Group 10.1038/icb.2015.62 <http://dx.doi.org/10.1038/icb.2015.62>

Palavras-Chave #610 Medicine & health
Tipo

info:eu-repo/semantics/article

info:eu-repo/semantics/publishedVersion

PeerReviewed