Function of Treg Cells Decreased in Patients With Systemic Lupus Erythematosus Due To the Effect of Prolactin

被引:29
作者
Victoria Legorreta-Haquet, Maria [1 ]
Chavez-Rueda, Karina [1 ]
Chavez-Sanchez, Luis [1 ]
Cervera-Castillo, Hernando [2 ]
Zenteno-Galindo, Edgar [3 ]
Barile-Fabris, Leonor [4 ]
Burgos-Vargas, Ruben [5 ]
Alvarez-Hernandez, Everardo [5 ]
Blanco-Favela, Francisco [1 ]
机构
[1] IMSS, CMN Siglo 12, Hosp Pediat, Unidad Invest Med Inmunol, Mexico City, DF, Mexico
[2] IMSS, Clin 25, Dept Reumatol, Mexico City, DF, Mexico
[3] Univ Nacl Autonoma Mexico, Dept Bioquim, Mexico City 04510, DF, Mexico
[4] Ctr Med Nacl Siglo XXI, Hosp Especialidades, Dept Reumatol, Mexico City, DF, Mexico
[5] Hosp Gen Mexico City, Serv Reumatol, Mexico City, DF, Mexico
关键词
TUMOR-NECROSIS-FACTOR; IN-VITRO; SUPPRESSION; EXPRESSION; DIFFERENTIATION; MECHANISMS; SENSITIVITY; ACTIVATION; CYTOKINE; ONSET;
D O I
10.1097/MD.0000000000002384
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Prolactin has different functions, including cytokine secretion and inhibition of the suppressor effect of regulatory T (T-reg) cells in healthy individuals. Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by defects in the functions of B, T, and T-reg cells. Prolactin plays an important role in the physiopathology of SLE. Our objective was to establish the participation of prolactin in the regulation of the immune response mediated by T-reg cells from patients with SLE. CD4(+)CD25(hi)CD127(-/low) cells were purified using magnetic beads and the relative expression of prolactin receptor was measured. The functional activity was evaluated by proliferation assay and cytokine secretion in activated cells, in the presence and absence of prolactin. We found that both percentage and function of T-reg cells decrease in SLE patients compared to healthy individuals with statistical significance. The prolactin receptor is constitutively expressed on T-reg and effector T (T-eff) cells in SLE patients, and this expression is higher than in healthy individuals. The expression of this receptor differs in inactive and active patients: in the former, the expression is higher in T-reg cells than in T-eff cells, similar to healthy individuals, whereas there is no difference in the expression between T-reg and T-eff cells from active patients. In T-reg:T-eff cell cocultures, addition of prolactin decreases the suppressor effect exerted by T-reg cells and increases IFN gamma secretion. Our results suggest that prolactin plays an important role in the activation of the disease in inactive patients by decreasing the suppressor function exerted by T-reg cells over T-eff cells, thereby favoring an inflammatory microenvironment.
引用
收藏
页数:9
相关论文
共 52 条
  • [1] CD161 expression characterizes a subpopulation of human regulatory T cells that produces IL-17 in a STAT3-dependent manner
    Afzali, Behdad
    Mitchell, Peter J.
    Edozie, Francis C.
    Povoleri, Giovanni A. M.
    Dowson, Sophie E.
    Demandt, Laura
    Walter, Gina
    Canavan, James B.
    Scotta, Cristiano
    Menon, Bina
    Chana, Prabhjoat S.
    Khamri, Wafa
    Kordasti, Shahram Y.
    Heck, Susanne
    Grimbacher, Bodo
    Tree, Timothy
    Cope, Andrew P.
    Taams, Leonie S.
    Lechler, Robert I.
    John, Susan
    Lombardi, Giovanna
    [J]. EUROPEAN JOURNAL OF IMMUNOLOGY, 2013, 43 (08) : 2043 - 2054
  • [2] Akiko O, 2011, J BIOMED BIOTECHNOL, V2011
  • [3] Regulatory T cells in patients with systemic lupus erythematosus
    Alvarado-Sanchez, Brenda
    Hernandez-Castro, Berenice
    Portales-Perez, Diana
    Baranda, Lourdes
    Layseca-Espinosa, Esther
    Abud-Mendoza, Carlos
    Cubillas-Tejeda, Ana C.
    Gonzalez-Amaro, Roberto
    [J]. JOURNAL OF AUTOIMMUNITY, 2006, 27 (02) : 110 - 118
  • [4] Phenotype, localization, and mechanism of suppression of CD4+CD25+ human thymocytes
    Annunziato, F
    Cosmi, L
    Liotta, F
    Lazzeri, E
    Manetti, R
    Vanini, V
    Romagnani, P
    Maggi, E
    Romagnani, S
    [J]. JOURNAL OF EXPERIMENTAL MEDICINE, 2002, 196 (03) : 379 - 387
  • [5] CD4+CD25+ regulatory T cells (TREG) in Systemic Lupus Erythematosus (SLE) patients:: The possible influence of treatment with corticosteroids
    Azab, N. A.
    Bassyouni, I. H.
    Emad, Y.
    El-Wahab, G. A. Abd
    Hamdy, G.
    Mashahit, M. A.
    [J]. CLINICAL IMMUNOLOGY, 2008, 127 (02) : 151 - 157
  • [6] Blanco-Favela F, 1999, J RHEUMATOL, V26, P55
  • [7] Prolactin (PRL) and its receptor: Actions, signal transduction pathways and phenotypes observed in PRL receptor knockout mice
    Bole-Feysot, C
    Goffin, V
    Edery, M
    Binart, N
    Kelly, PA
    [J]. ENDOCRINE REVIEWS, 1998, 19 (03) : 225 - 268
  • [8] Quantitative and qualitative deficiencies of regulatory T cells in patients with systemic lupus erythematosus (SLE)
    Bonelli, Michael
    Savitskaya, Anastasia
    von Dalwigk, Karolina
    Steiner, Carl Walter
    Aletaha, Daniel
    Smolen, Josef S.
    Scheinecker, Clemens
    [J]. INTERNATIONAL IMMUNOLOGY, 2008, 20 (07) : 861 - 868
  • [9] Lower proportions of CD4+CD25high and CD4+FoxP3, but not CD4+CD25+CD127low FoxP3+T cell levels in children with autoimmune thyroid diseases
    Bossowski, A.
    Moniuszko, M.
    Dabrowska, M.
    Sawicka, B.
    Rusak, M.
    Jeznach, M.
    Wojtowicz, J.
    Bodzenta-Lukaszyk, A.
    Bossowska, A.
    [J]. AUTOIMMUNITY, 2013, 46 (03) : 222 - 230
  • [10] Cutting Edge: The Th1 Response Inhibits the Generation of Peripheral Regulatory T Cells
    Caretto, David
    Katzman, Shoshana D.
    Villarino, Alejandro V.
    Gallo, Eugenio
    Abbas, Abul K.
    [J]. JOURNAL OF IMMUNOLOGY, 2010, 184 (01) : 30 - 34