Estradiol promotes functional responses in inflammatory and steady-state dendritic cells through differential requirement for activation function-1 of estrogen receptor α
- PMID: 23626011
- DOI: 10.4049/jimmunol.1203312
Estradiol promotes functional responses in inflammatory and steady-state dendritic cells through differential requirement for activation function-1 of estrogen receptor α
Abstract
17β-Estradiol (E2) has been shown to regulate GM-CSF- or Flt3 ligand-driven dendritic cell (DC) development through estrogen receptor (ER) α signaling in myeloid progenitors. ERα regulates transcription of target genes through two distinct activation functions (AFs), AF-1 and AF-2, whose respective involvement varies in a cell type- or tissue-specific manner. In this study, we investigated the role of ERα AFs in the development and effector functions of inflammatory DCs, steady-state conventional DCs, and plasmacytoid DCs (pDC), using mouse lacking either AF-1 or AF-2. In agreement with previous works, we showed that E2 fostered the differentiation and effector functions of inflammatory DCs through ERα-dependent upregulation of IFN regulatory factor (IRF)-4 in GM-CSF-stimulated myeloid progenitors. Interestingly, whereas AF-1 was required for early IRF-4 upregulation in DC precursors, it was dispensable to enhance IRF-4 expression in differentiated DCs to a level compatible with the development of the more functional Ly6C(-) CD11b(+) DC subset. Presence of E2 had no effect on progenitors from either knock-in mice with 7-aa deletion in helix 12 of ERα, lacking AF-2, or ERα(-/-) mice. By contrast, in Flt3 ligand-driven DC differentiation, activation of AF-1 domain was required to promote the development of more functionally competent conventional DCs and pDCs. Moreover, lack of ERα AF-1 blunted the TLR7-mediated IFN-α response of female pDCs in vivo. Thus, our study demonstrates that ERα uses AF-1 differently in steady-state and inflammatory DC lineages to regulate their innate functions, suggesting that selective ER modulators could be used to target specific DC subsets.
Similar articles
-
Estradiol acts directly on bone marrow myeloid progenitors to differentially regulate GM-CSF or Flt3 ligand-mediated dendritic cell differentiation.J Immunol. 2008 Jan 15;180(2):727-38. doi: 10.4049/jimmunol.180.2.727. J Immunol. 2008. PMID: 18178810
-
Estrogen receptor alpha, but not beta, is required for optimal dendritic cell differentiation and [corrected] CD40-induced cytokine production.J Immunol. 2008 Mar 15;180(6):3661-9. doi: 10.4049/jimmunol.180.6.3661. J Immunol. 2008. PMID: 18322171
-
Estrogen receptor signaling promotes dendritic cell differentiation by increasing expression of the transcription factor IRF4.Blood. 2010 Jan 14;115(2):238-46. doi: 10.1182/blood-2009-08-236935. Epub 2009 Oct 30. Blood. 2010. PMID: 19880499 Free PMC article.
-
Estrogen receptors regulate an inflammatory pathway of dendritic cell differentiation: mechanisms and implications for immunity.Horm Behav. 2012 Aug;62(3):254-62. doi: 10.1016/j.yhbeh.2012.04.011. Epub 2012 Apr 25. Horm Behav. 2012. PMID: 22561458 Free PMC article. Review.
-
Estrogen Receptor-Dependent Regulation of Dendritic Cell Development and Function.Front Immunol. 2017 Feb 10;8:108. doi: 10.3389/fimmu.2017.00108. eCollection 2017. Front Immunol. 2017. PMID: 28239379 Free PMC article. Review.
Cited by
-
Hepatic immune regulation and sex disparities.Nat Rev Gastroenterol Hepatol. 2024 Sep 5. doi: 10.1038/s41575-024-00974-5. Online ahead of print. Nat Rev Gastroenterol Hepatol. 2024. PMID: 39237606 Review.
-
Are Gender Differences Important for Autoimmune Liver Diseases?Life (Basel). 2024 Apr 12;14(4):500. doi: 10.3390/life14040500. Life (Basel). 2024. PMID: 38672770 Free PMC article. Review.
-
Reduction of IFN-I responses by plasmacytoid dendritic cells in a longitudinal trans men cohort.iScience. 2023 Oct 13;26(11):108209. doi: 10.1016/j.isci.2023.108209. eCollection 2023 Nov 17. iScience. 2023. PMID: 37953956 Free PMC article.
-
The Influence of Sex Hormones and X Chromosome in Immune Responses.Curr Top Microbiol Immunol. 2023;441:21-59. doi: 10.1007/978-3-031-35139-6_2. Curr Top Microbiol Immunol. 2023. PMID: 37695424 Review.
-
Sex bias in lymphocytes: Implications for autoimmune diseases.Front Immunol. 2022 Nov 24;13:945762. doi: 10.3389/fimmu.2022.945762. eCollection 2022. Front Immunol. 2022. PMID: 36505451 Free PMC article. Review.
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Other Literature Sources
Molecular Biology Databases
Research Materials
Miscellaneous