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

被引:33
作者
Aristimuno, Carol [1 ]
Teijeiro, Roseta [1 ]
Valor, Lara [1 ]
Alonso, Barbara [1 ]
Tejera-Alhambra, Marta [1 ]
de Andres, Clara [2 ]
Oliver Minarro, Desamparados [1 ]
Lopez-Lazareno, Nieves [3 ]
Faure, Florence [4 ]
Sanchez-Ramon, Silvia [1 ]
机构
[1] Hosp Gen Univ Gregorio Maranon, Dept Immunol, Madrid 28007, Spain
[2] Hosp Gen Univ Gregorio Maranon, Dept Neurol, Madrid 28007, Spain
[3] Hosp Gen Univ Gregorio Maranon, Dept Biochem, Madrid 28007, Spain
[4] Inst Curie, INSERM U932, Paris, France
关键词
Multiple sclerosis; Sex hormones; Oestradiol receptors; Regulatory T-cells; EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS; CIRCULATING DENDRITIC CELLS; ESTROGEN-RECEPTORS; PERFORIN EXPRESSION; IN-VITRO; EX-VIVO; PREGNANCY; PROGESTERONE; ESTRADIOL; EXPANSION;
D O I
10.1007/s10238-011-0172-3
中图分类号
R-3 [医学研究方法]; R3 [基础医学];
学科分类号
1001 ;
摘要
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 (T-Reg). Given that alterations in T-Reg proportions and suppressive function are involved in MS pathophysiology, we investigated the in vitro effect of sex hormones on T-Reg. Here, we show that both E2 and progesterone (P2) enhance T-Reg function in vitro, although only E2 further induces a T-Reg phenotype in activated responder T-cells (CD4(+)CD25(-)) (P < 0.01). E2 receptor beta (ER beta) percentages and mean fluorescence intensity (MFI) on T-Reg 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 ER beta were higher in T-Reg 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 T-Reg, which may be relevant for the in vivo responsiveness of these cells to sex hormones and hence to MS physiopathology.
引用
收藏
页码:247 / 255
页数:9
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