Editing Estrogen (section)

===Immune system===
The effect of estrogen on the [[immune system]] is in general described as [[Th2]] favoring, rather than suppressive, as is the case of the effect of male sex hormone – testosterone.<ref name="Foo_et_al_2016">{{cite journal | vauthors = Foo YZ, Nakagawa S, Rhodes G, Simmons LW | title = The effects of sex hormones on immune function: a meta-analysis | journal = Biological Reviews of the Cambridge Philosophical Society | volume = 92 | issue = 1 | pages = 551–571 | date = February 2017 | pmid = 26800512 | doi = 10.1111/brv.12243 | s2cid = 37931012 | url = https://api.research-repository.uwa.edu.au/ws/files/21601252/Foo_et_al_2017_The_effects_of_sex_hormones_on_immune_function_a_meta_analysis.pdf }}</ref> Indeed, women respond better to [[vaccine]]s, [[infection]]s and are generally less likely to develop [[cancer]], the tradeoff of this is that they are more likely to develop an [[autoimmune disease]].<ref name="Taneja_2018">{{cite journal | vauthors = Taneja V | title = Sex Hormones Determine Immune Response | journal = Frontiers in Immunology | volume = 9 | pages = 1931 | date = 27 August 2018 | pmid = 30210492 | doi = 10.3389/fimmu.2018.01931 | pmc = 6119719 | doi-access = free }}</ref> The [[Th2]] shift manifests itself in a decrease of cellular immunity and increase in humoral immunity ([[antibody]] production) shifts it from cellular to humoral by downregulating cell-mediated immunity and enhancing Th2 immune response by stimulating IL-4 production and Th2 differentiation.<ref name="Foo_et_al_2016"/><ref name="Roved_et_al_2017">{{cite journal | vauthors = Roved J, Westerdahl H, Hasselquist D | title = Sex differences in immune responses: Hormonal effects, antagonistic selection, and evolutionary consequences | journal = Hormones and Behavior | volume = 88 | pages = 95–105 | date = February 2017 | pmid = 27956226 | doi = 10.1016/j.yhbeh.2016.11.017 | s2cid = 9137227 }}</ref> [[Th1 cell|Type 1]] and [[Th17|type 17]] immune responses are downregulated, likely to be at least partially due to [[Interleukin 4|IL-4]], which inhibits Th1. Effect of estrogen on different immune cells' cell types is in line with its Th2 bias. Activity of [[basophil]]s, [[eosinophil]]s, M2 [[macrophage]]s and is enhanced, whereas activity of [[NK cell]]s is downregulated. Conventional [[dendritic cell]]s are biased towards Th2 under the influence of estrogen, whereas plasmacytoid dendritic cells, key players in antiviral defence, have increased [[IFN-g]] secretion.<ref name="Roved_et_al_2017"/> Estrogen also influences [[B cell]]s by increasing their survival, proliferation, differentiation and function, which corresponds with higher antibody and B cell count generally detected in women.<ref name="Khan_Ansar_2016">{{cite journal | vauthors = Khan D, Ansar Ahmed S | title = The Immune System Is a Natural Target for Estrogen Action: Opposing Effects of Estrogen in Two Prototypical Autoimmune Diseases | journal = Frontiers in Immunology | volume = 6 | pages = 635 | date = 6 January 2016 | pmid = 26779182 | doi = 10.3389/fimmu.2015.00635 | pmc = 4701921 | doi-access = free }}</ref>

On a molecular level estrogen induces the above-mentioned effects on cell via acting on intracellular [[Receptor (biochemistry)|receptors]] termed ER α and ER β, which upon ligation form either homo or heterodimers. The genetic and nongenetic targets of the receptors differ between homo and heterodimers.<ref name="Kovats_2015">{{cite journal | vauthors = Kovats S | title = Estrogen receptors regulate innate immune cells and signaling pathways | journal = Cellular Immunology | volume = 294 | issue = 2 | pages = 63–69 | date = April 2015 | pmid = 25682174 | doi = 10.1016/j.cellimm.2015.01.018 | pmc = 4380804 }}</ref> Ligation of these receptors allows them to translocate to the [[Cell nucleus|nucleus]] and act as [[transcription factor]]s either by binding estrogen response elements (ERE) on [[DNA]] or binding DNA together with other transcriptional factors e.g. [[Nf-kB]] or [[Activator protein 1|AP-1]], both of which result in [[RNA polymerase]] recruitment and further [[chromatin remodelation]].<ref name="Kovats_2015"/> A non-transcriptional response to oestrogen stimulation was also documented (termed membrane-initiated steroid signalling, MISS). This pathway stimulates the ERK and PI3K/AKT pathways, which are known to increase cellular proliferation and affect chromatin remodelation.<ref name="Kovats_2015"/>