Natural Killer Cells Express Estrogen Receptor-α and Estrogen Receptor-β and Can Respond to Estrogen Via a Non-Estrogen Receptor-α-Mediated Pathway

Curran, Edward M.; Berghaus, Londa J.; Vernetti, Nicholas J.; Saporita, Anthony J.; Lubahn, Dennis B.; Estes, D. Mark

doi:10.1006/cimm.2002.1886

Cited by 116 publications

(83 citation statements)

References 56 publications

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“…It exerts many genomic and nongenomic effects through binding to the intracellular or membrane receptor proteins (7). Estrogen receptor α (ERα) and ERβ have been recently identified in mouse splenic NK cells (8). It suggests that E2 may be involved in the regulation of NK cell functions.…”

Section: Introductionmentioning

confidence: 99%

17β-Estradiol Suppresses Cytotoxicity and Proliferative Capacity of Murine Splenic NK1.1+ Cells

Hao

Zhao

et al. 2008

Cell Mol Immunol

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In order to clarify the effects of 17β-estradiol (E2) on natural killer (NK) cells and the possibly regulatory mechanisms, we obtained highly purified and viable NK cells from C57BL/6J mouse spleen by a magnetic cell sorter (MACS). These cells were treated with E2 and then their cytotoxicity and proliferative capacity were examined. To further investigate the mechanisms on the effect of E2 on NK cells, expressions of activationassociated markers (CD69, CD122) and inhibitory receptors (CD94, Ly49), and intracellular cytokine production were analyzed. At last, we performed the cDNA microarray to explore the possible involved genes. We found that E2 could suppress NK cell cytotoxicity and proliferative capacity in vitro. E2 reduced NK cell cytotoxicity and proliferative capacity, which may be through influencing the phenotypes and cytokine expression of NK cells, mainly involving CD94 and IFN-γ. Furthermore, regulation of Stat4, Fyn, Sh2d1a, Eat2, Cd244, Irf1, Runx1, Irf7, Irf5, Esrra and Nr5a1 genes may be related to the cytotoxicity, proliferation and cytokine production of E2-mediated purified NK cells. Cellular & Molecular Immunology. 2008;5(5):357-364.

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Section: Introductionmentioning

confidence: 99%

17β-Estradiol Suppresses Cytotoxicity and Proliferative Capacity of Murine Splenic NK1.1+ Cells

Hao

Zhao

et al. 2008

Cell Mol Immunol

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“…Receptory androgenowe stwierdzono w limfocytach B i T oraz w makrofagach [9]. Z kolei receptory estrogenowe są obecne w limfocytach B i T, komórkach dendrytycznych, neutrofilach, makrofagach, komórkach NK, komórkach macierzy grasicy, komórkach szpiku kostnego, a także w komórkach endotelialnych [7,10,11]. Obydwa znane rodzaje receptorów estrogenowych: alfa i beta wykazują zróżnicowaną ekspresję w różnych komórkach układu odpornościowego [7].…”

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Sex and autoimmune thyroid diseases

Kucharská¹

2014

Pediatr. Endocrinol.

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STRESZCZENIE/ABSTRACTAutoimmunizacyjne choroby tarczycy (AIChT) występują znacznie częściej u kobiet niż u mężczyzn, co sugeruje, że dla ich rozwoju istotne znaczenie mają czynniki związane z płcią. Ustalono, że istnieje wyraźny dymorfizm płciowy układu immunologicznego. U kobiet stwierdza się wyższą liczbę limfocytów CD4+, zwiększony stosunek subpopulacji CD4+ do CD8+ i preferencję odpowiedzi zależnej od Th2. U mężczyzn z kolei stwierdza się wyższą aktywność komórek NK oraz preferencję odpowiedzi zależnej od Th1. Podobne zjawiska zaobserwowano na zwierzęcych modelach doświadczalnych. Istnieje wiele hipotez, które mają wyjaśnić potencjalne przyczyny zwiększonej podatności płci żeńskiej na AIChT. Wśród nich za najistotniejsze uważa się czynniki genetyczne związane z chromosomami płciowymi. Na chromosomie X są zlokalizowane geny ważne dla regulacji odpowiedzi immunologicznej: m.in. Foxp3 (Xp11.23), CD40L (Xq26), BTK (Xq21.33-q22), IL2RG (Xq13.1), XIAP (Xq25). Sugeruje się także znaczenie ukierunkowanej inaktywacji drugiego chromosomu X, która występuje częściej u kobiet z autoimmunizacyjnymi chorobami tarczycy. Kolejnym możliwym czynnikiem jest zjawisko mikrochimeryzmu płodowego, który stwierdza się częściej u kobiet z AIChT. Znaczenie może mieć również zaburzenie funkcji microRNA (miRNA), które jest istotnym regulatorem odpowiedzi immunologicznej, a chromosom X zawiera aż 10% całego miRNA genomowego. Wydaje się także, że chromosom Y może pełnić rolę protekcyjną. Endokrynol. Ped. 13/2014;2(47):57-64.Autoimmune thyroid diseases (AITD) are much more frequent in female than male. This fact suggests a strong influence of sex dependent factors in AITD development. It was confirmed that immune system function is dimorphic in male and female. In females there is increased number of CD4+ T cells, increased proportion of CD4+ cells to CD8+cells and preferential Th2-dependent immune response. In males the activity of NK cells is increased and Th1-dependent immune response is preferential. Similar phenomena were observed in experimental animal models. Many theories arise to explain the reason of increased susceptibility to AITD in female. As the most important are considered genetic factors linked to sex chromosomes. On the X chromosome are located genes important for immune response regulation, i. e. Foxp3 (Xp11.23), CD40L (Xq26), BTK (Xq21.33-q22), IL2RG (Xq13.1), XIAP (Xq25). Additionally

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“…The cellular response to estrogen can be mediated by the estrogen receptor (ER), which is expressed on immune cells, such as T cells and B cells, as well as dendritic cells (DCs) (4)(5)(6)(7)(8)(9). The presence of ERs on DCs indicates the possibility that 17␤-estradiol directly modulates DC functions.…”

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confidence: 99%

17β‐estradiol induces CD40 expression in dendritic cells via MAPK signaling pathways in a minichromosome maintenance protein 6–dependent manner

Xie

Hua

Sun

et al. 2011

Arthritis & Rheumatism

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Objective. The human immune system exhibits sexual dimorphism in autoimmune diseases such as systemic lupus erythematosus (SLE). Female sex hormones, including 17␤-estradiol, are strongly implicated in the gender bias in SLE. CD40 is a costimulatory molecule and plays a crucial role in modulating the immune response of effector cells. We have previously shown that 17␤-estradiol up-regulated CD40 expression and altered minichromosome maintenance protein 6 (MCM6) gene expression in dendritic cells (DCs). The mechanism of the correlation between CD40 and MCM6 in the presence of 17␤-estradiol remains unknown. This study was undertaken to elucidate this mechanism and to explain the role of MCM6 in the gender bias in SLE.Methods. Bone marrow-derived DCs transfected with small interfering RNA (siRNA) for MCM6 were treated with 17␤-estradiol in the absence or presence of CpG. The expression levels of costimulatory molecules, activity of MAPKs, and levels of MCM6 protein were measured. Moreover, the functions of DCs, including proliferation, apoptosis, endocytosis, and cytokine production, were analyzed. In addition, levels of messenger RNA for MCM6 were detected in DCs purified from SLE patients.Results. Regardless of the presence or absence of CpG, 17␤-estradiol induced CD40 expression via the activation of p38 and JNK, but not ERK. The activation of p38 and JNK enhanced MCM6 expression, which then induced CD40 expression. Suppression of MCM6 in DCs abolished the up-regulation of 17␤-estradiolinduced CD40 expression. Importantly, MCM6 expression was significantly increased in SLE patients compared with healthy controls.Conclusion. Our findings indicate that 17␤-estradiol induces CD40 expression in DCs via p38 and JNK MAPKs in an MCM6-dependent manner. MCM6 may be a critical mediator of sex-based differences in autoimmune disease.

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Natural Killer Cells Express Estrogen Receptor-α and Estrogen Receptor-β and Can Respond to Estrogen Via a Non-Estrogen Receptor-α-Mediated Pathway

Cited by 116 publications

References 56 publications

17β-Estradiol Suppresses Cytotoxicity and Proliferative Capacity of Murine Splenic NK1.1+ Cells

17β-Estradiol Suppresses Cytotoxicity and Proliferative Capacity of Murine Splenic NK1.1+ Cells

Sex and autoimmune thyroid diseases

17β‐estradiol induces CD40 expression in dendritic cells via MAPK signaling pathways in a minichromosome maintenance protein 6–dependent manner

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