title: Immune cell-mediated neuroprotection is independent of estrogen action through estrogen receptor-alpha.
abstract: It has been well documented that both estrogen and immune cells (CD4+ T cells) mediate neuroprotection in the mouse facial nerve axotomy model. Estrogen has been shown to play an important role in regulating the immune response. However, it is unclear whether immune cell-mediated neuroprotection is dependent on estrogen signaling. In this study, using FACS staining, we confirmed that the majority of CD4+ T cells express high levels of estrogen receptor-alpha (ERα), suggesting that CD4+ T cell-mediated neuroprotection may be modulated by estrogen signaling. We previously found that immunodeficient Rag-2KO mice showed a significant increase in axotomy-induced facial motoneuron death compared to immunocompetent wild-type mice. Therefore, we investigated axotomy-induced facial motoneuron loss in immunodeficient Rag-2KO mice that received 17β-estradiol treatment or adoptive transfer of immune cells from mice lacking functional ERα. Our results indicate that while estradiol treatment failed to rescue facial motoneurons from axotomy-induced cell death in Rag-2KO mice, immune cells lacking ERα successfully restored facial motoneuron survival in Rag-2 KO mice to a wild-type level. Collectively, we concluded that CD4+ T cell-mediated neuroprotection is independent of estrogen action through ERα.
authors: Neuroscience Institute, Loyola University Medical Center, 2160 South First Avenue, Maywood, IL 60153, USA. neuroimmune@gmail.com
authors: Junping
authors: J
authors: Xin
authors: Keith N
authors: KN
authors: Fargo
authors: Lisa
authors: L
authors: Tanzer
authors: Virginia M
authors: VM
authors: Sanders
authors: Kathryn J
authors: KJ
authors: Jones
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D019771:Axotomy / Q000379:methods; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D002450:Cell Communication / Q000276:immunology; D002470:Cell Survival / Q000276:immunology / Q000502:physiology; D004268:DNA-Binding Proteins / Q000276:immunology / Q000378:metabolism; D004195:Disease Models, Animal; D004958:Estradiol / Q000494:pharmacology; D047628:Estrogen Receptor alpha / Q000276:immunology / Q000378:metabolism*; D004967:Estrogens / Q000378:metabolism*; D005154:Facial Nerve / Q000276:immunology / Q000473:pathology / Q000601:surgery; D020220:Facial Nerve Injuries / Q000276:immunology / Q000473:pathology*; D005260:Female; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009046:Motor Neurons / Q000166:cytology / Q000276:immunology / Q000378:metabolism / Q000502:physiology*; D015398:Signal Transduction
chemical_list: D004268:DNA-Binding Proteins; D047628:Estrogen Receptor alpha; D004967:Estrogens; C499308:Rag2 protein, mouse; D004958:Estradiol