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Sex-hormone receptors pattern on regulatory T-cells: clinical implications for multiple sclerosis

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Abstract

Cellular mechanisms underlying sexual dimorphism in the immune response remain largely unknown. Concerning the interactions among the nervous, endocrine and immune systems, we reported that during gestation, a period during which multiple sclerosis (MS) clearly ameliorates, there is a physiological expansion of regulatory T-lymphocytes (TReg). Given that alterations in TReg proportions and suppressive function are involved in MS pathophysiology, we investigated the in vitro effect of sex hormones on TReg. Here, we show that both E2 and progesterone (P2) enhance TReg function in vitro, although only E2 further induces a TReg phenotype in activated responder T-cells (CD4+CD25) (P < 0.01). E2 receptor beta (ERβ) percentages and mean fluorescence intensity (MFI) on TReg were lower in MS patients than in controls (P < 0.05), in parallel with lower E2 plasma levels (P < 0.05). Importantly, percentages and MFI of ERβ were higher in TReg than in T-responder cells (P < 0.0001) both in MS patients and controls. We show a unique differential pattern of higher ER and PR levels in TReg, which may be relevant for the in vivo responsiveness of these cells to sex hormones and hence to MS physiopathology.

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Acknowledgments

We would like to thank Dr. Paloma Sánchez-Mateos and Dr. Jonathan Poznansky for critical reading of the manuscript. We thank the patients and healthy volunteers who provided blood samples, Julia Parra and Piedad Calvo for technical assistance, and José M Bellón for statistical help. This study was supported by grant PI 040468 from the Fondo de Investigación Sanitaria, Instituto de Salud Carlos III, by grant from Fundación Alicia Koplowitz to SS.

Conflict of interest

There is no potential financial interest. We provide original and clinically relevant data on the physiopathology of multiple sclerosis and thus in autoimmune disease.

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Correspondence to Silvia Sánchez-Ramón.

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Carol Aristimuño and Roseta Teijeiro have equally contributed to this work.

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Aristimuño, C., Teijeiro, R., Valor, L. et al. Sex-hormone receptors pattern on regulatory T-cells: clinical implications for multiple sclerosis. Clin Exp Med 12, 247–255 (2012). https://doi.org/10.1007/s10238-011-0172-3

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