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Journal articles
Estrogen receptor alpha, but not beta, is required for optimal dendritic cell differentiation and [corrected] CD40-induced cytokine production.: Estrogen receptor alpha is required for optimal dendritic cell development
Abstract : Dendritic cells (DC) are critical actors in the initiation of primary immune responses and regulation of self-tolerance. The steroid sex hormone 17beta-estradiol (E(2)) has been shown to promote the differentiation of DCs from bone marrow (BM) precursors in vitro. However, the estrogen receptor (ER) involved in this effect has not yet been characterized. Using recently generated ERalpha- or ERbeta-deficient mice, we investigated the role of ER isotypes in DC differentiation and acquisition of effector functions. We report that estrogen-dependent activation of ERalpha, but not ERbeta, is required for normal DC development from BM precursors cultured with GM-CSF. We show that reduced numbers of DCs were generated in the absence of ERalpha activation and provide evidence for a cell-autonomous function of ERalpha signaling in DC differentiation. ERalpha-deficient DCs were phenotypically and functionally distinct from wild-type DCs generated in the presence of estrogens. In response to microbial components, ERalpha-deficient DCs failed to up-regulate MHC class II and CD86 molecules, which could account for their reduced capacity to prime naive CD4(+) T lymphocytes. Although they retained the ability to express CD40 and to produce proinflammatory cytokines (e.g., IL-12, IL-6) upon TLR engagement, ERalpha-deficient DCs were defective in their ability to secrete such cytokines in response to CD40-CD40L interactions. Taken together, these results provide the first genetic evidence that ERalpha is the main receptor regulating estrogen-dependent DC differentiation in vitro and acquisition of their effector functions.
Cited literature [15 references]
https://www.hal.inserm.fr/inserm-00312757
Contributor : Jean-Charles Guéry <>
Submitted on : Friday, March 13, 2009 - 10:38:43 AM
Last modification on : Thursday, April 23, 2020 - 2:26:26 PM
Long-term archiving on: : Thursday, June 3, 2010 - 5:21:29 PM
Contributor : Jean-Charles Guéry <>
Submitted on : Friday, March 13, 2009 - 10:38:43 AM
Last modification on : Thursday, April 23, 2020 - 2:26:26 PM
Long-term archiving on: : Thursday, June 3, 2010 - 5:21:29 PM
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