Estradiol enhances capacity of TLR-matured splenic dendritic cells to polarize CD4+ lymphocytes into IL-17/GM-CSF-producing cells in vitro.
There are little data on modulatory effects of estrogens on rat dendritic cell (DC) responses to inflammatory stimuli, and consequently their ability to activate and polarize CD4+ T lymphocyte-mediated immune responses. Splenic conventional DCs from young female Albino Oxford rats were activated in vitro with LPS (TLR4 agonist) or R848 (TLR7/8 agonist) in the presence and absence of 17β-estradiol (E2), and their allostimulatory and CD4+ lymphocyte polarizing ability in mixed leukocyte culture (MLC) were studied. Irrespective of the E2 presence, LPS and R848 up-regulated the expression of MHC II on DCs, so they exhibited enhanced allostimulatory capacity in co-culture with CD4+ lymphocytes. On the other hand, E2 promoted stimulatory action of both TLRs on OX62+ DC IL-23 production, augmented their stimulatory effects on IL-6 and IL-1β production, but diminished their enhancing effects on the expression IL-10 and IL-27 by DCs. Consequently, in MLC, OX62+ DCs activated/matured in the co-presence of E2 and either LPS or R848 increased the levels of IL-17, the signature Th17 cell cytokine, when compared with those activated/matured in the absence of E2. GM-CSF levels were also increased in these MLC. Given that the expression of IL-7 mRNA was diminished in DCs activated/matured in the co-presence of E2 and TLR, this increase most likely did not reflect enhanced differentiation of Th cells producing GM-CSF only (Th-GM).


CONCLUSIONS
E2 augments capacity of LPS- and R848-activated/matured DCs from young rat spleen to induce differentiation of IL-17- and GM-CSF-producing cells.
Department of Microbiology and Immunology, Faculty of Pharmacy, University of Belgrade, Belgrade, Serbia.
Zorica
Z
Stojić-Vukanić
Department of Microbiology and Immunology, Faculty of Pharmacy, University of Belgrade, Belgrade, Serbia.
Biljana
B
Bufan
Immunology Research Center "Branislav Janković", Institute of Virology, Vaccines and Sera "Torlak", Belgrade, Serbia.
Ivan
I
Pilipović
Immunology Research Center "Branislav Janković", Institute of Virology, Vaccines and Sera "Torlak", Belgrade, Serbia.
Ivana
I
Vujnović
Department of Physiology, Faculty of Pharmacy, University of Belgrade, Belgrade, Serbia.
Mirjana
M
Nacka-Aleksić
Immunology Research Center "Branislav Janković", Institute of Virology, Vaccines and Sera "Torlak", Belgrade, Serbia.
Raisa
R
Petrović
Department of Microbiology and Immunology, Faculty of Pharmacy, University of Belgrade, Belgrade, Serbia.
Nevena
N
Arsenović-Ranin
Department of Physiology, Faculty of Pharmacy, University of Belgrade, Belgrade, Serbia. Electronic address: Gordana.Leposavic@pharmacy.bg.ac.rs.
Gordana
G
Leposavić
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects* / Q000378:metabolism; D002478:Cells, Cultured; D018920:Coculture Techniques; D016207:Cytokines / Q000235:genetics / Q000378:metabolism*; D003713:Dendritic Cells / Q000187:drug effects* / Q000378:metabolism; D004958:Estradiol / Q000494:pharmacology*; D004967:Estrogens / Q000494:pharmacology*; D005260:Female; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D013154:Spleen / Q000166:cytology; D051193:Toll-Like Receptors / Q000378:metabolism*
D016207:Cytokines; D004967:Estrogens; D012333:RNA, Messenger; D051193:Toll-Like Receptors; D004958:Estradiol
Conventional dendritic cell polarizing ability; Estradiol; LPS; Mixed leukocyte culture; R848