Sex-hormone receptors pattern on regulatory T-cells: clinical implications for multiple sclerosis.
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 (ERβ) 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 ERβ 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.
Department of Immunology, Hospital General Universitario Gregorio Marañón, Doctor Esquerdo 46, 28007 Madrid, Spain.
Carol
C
Aristimuño
Roseta
R
Teijeiro
Lara
L
Valor
Bárbara
B
Alonso
Marta
M
Tejera-Alhambra
Clara
C
de Andrés
Desamparados Oliver
DO
Miñarro
Nieves
N
López-Lazareno
Florence
F
Faure
Silvia
S
Sánchez-Ramón
D004958:Estradiol / Q000378:metabolism*; D047629:Estrogen Receptor beta / Q000032:analysis*; D006728:Hormones; D006801:Humans; D008297:Male; D009103:Multiple Sclerosis / Q000473:pathology*; D011374:Progesterone / Q000378:metabolism; D050378:T-Lymphocytes, Regulatory / Q000378:metabolism*
D047629:Estrogen Receptor beta; D006728:Hormones; D011374:Progesterone; D004958:Estradiol