Extracorporeal Photopheresis Differentially Regulates the Expression of Phosphorylated STAT-1 and STAT-5 in Treated Monocytes and T cells, Respectively

Basic/Clinical Science

Abstract

Background

Extracorporeal photopheresis (ECP) is effective in conditions with opposing immune etiology. ECP induces an immunomodulatory response through simultaneous monocyte activation and apoptosis induction of lymphocytes. However, ECP is also immunosuppressive, downregulating proinflammatory cytokines. Signal transducers and activators of transcription (STATs) are important mediators of cell-signaling systems, including cytokines. Ultraviolet (UV) immunosuppression is linked to reductions in cytokine-induced STAT phosphorylation.

Objective

The aim of this study was to find whether ECP downregulates STAT phosphorylation.

Methods

Pre- and post-ECP mononuclear cells from cutaneous T-cell lymphoma and chronic graft-versus-host disease patients were stimulated with either IFNβ, IL2, or IL15. The percentage of IFNβ-stimulated monocytes positive for phosphorylated STAT-1 (pSTAT-1) and the number of IL2- and IL15-stimulated T cells expressing phosphorylated STAT-5 (pSTAT-5) were determined at 0 and 24 h.

Results

Post-ECP, pSTAT-1 levels in monocytes remained unchanged; however, at 24 h post-ECP the number of T cells expressing pSTAT-5 was reduced.

Conclusion

Following ECP, monocytes retain their ability to phosphorylate STAT-1, while pSTAT-5 expression is lost in lymphocytes. This differential effect of ECP may account for the diverse population of diseases that benefit.

Keywords

Chronic GvHD Apoptotic Lymphocyte Pretransplant Conditioning Extracorporeal Photopheresis CTCL Patient 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Sommaire

Antécédents

La photophérèse extracorporelle est efficace en présence de conditions ayant une étiologie immunitaire. La photophérèse extracorporelle produit une réponse immunomodulatrice grâce à, simultanément, une activation des monocytes et une induction de l’apoptose dans les lymphocytes. Toutefois, la photophérèse extracorporelle a également des caractéristiques immunosuppressives qui régularisent à la baisse les cytokines proinflammatoires. Les signaux transducteurs et activateurs de la transcription (STAT) sont d’importants médiateurs des systémes de signalisation cellulaire, y compris les cytokines. L’immunosuppression par rayons UV est liée à une réduction de la phosphorylation des STAT causée par les cytokines.

Objectif

Découvrir si la photophérèse extracorporelle régularise à la baisse la phosphorylation des STAT.

Méthode

Des cellules mononucléaires, pré et post photophérèse extracorporelle, prises de lymphomes T et de greffes chroniques ont été stimulées par IFNβ, IL2 ou IL15. Le pourcentage de monocytes stimulés au IFNβ qui ont exprimé des STAT-1 phosphorylés (pSTAT-1) et le nombre de cellules T stimulées au IL2 et au IL15qui ont exprimé des STAT-5 phosphorylés (pSTAT-5) ont été prélevés aux heures 0 et 24.

Résultats

Le niveau de monocytes pSTAT-1 post-photophérèse extracorporelle est resté inchangé; 24 heures après la photophérèse extracorporelle, le nombre de cellules T exprimant pSTAT-5 a baissé.

Conclusion

À la suite de la photophérèse extracorporelle, les monocytes conservent leur capacité de phosphoryler STAT-1, alors que l’expression de pSTAT-5 se perd en lymphocytes. Cet effet différentiel de la photophérèse extracorporelle pourrait expliquer le nombre variant de maladies qui en profitent.

Notes

Acknowledgments

We would like to thank Dr. A. MacWhannel, Prof. N.H. Russell, Dr. S. Littlewood, Dr. G. Cook, Dr. P. Mahendra, Dr. J. Snowdon, and Dr. E. Bessell for referring patients to the photopheresis unit at Rotherham General Hospital. Thanks also go to Barry Farmer for helping prepare the illustrations and to all the patients and nursing staff of the photopheresis unit for their assistance with this study.

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Copyright information

© Springer-Verlag 2004

Authors and Affiliations

  1. 1.Department of HaematologyRotherham General HospitalSouth YorkshireUnited Kingdom

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