PDF(Pubmed)
Abstract：
BACKGROUND: Key to the advancement of the field of bioelectronic medicine is the identification of novel pathways of neural regulation of immune function. Sensory neurons (termed nociceptors) recognize harmful stimuli and initiate a protective response by eliciting pain and defensive behavior. Nociceptors also interact with immune cells to regulate host defense and inflammatory responses. However, it is still unclear whether nociceptors participate in regulating primary IgG antibody responses to novel antigens.
METHODS: To understand the role of transient receptor potential vanilloid 1 (TRPV1)-expressing neurons in IgG responses, we generated TRPV1-Cre/Rosa-ChannelRhodopsin2 mice for precise optogenetic activation of TRPV1 + neurons and TRPV1-Cre/Lox-diphtheria toxin A mice for targeted ablation of TRPV1-expressing neurons. Antigen-specific antibody responses were longitudinally monitored for 28 days.
RESULTS: Here we show that TRPV1 expressing neurons are required to develop an antigen-specific immune response. We demonstrate that selective optogenetic stimulation of TRPV1+ nociceptors during immunization significantly enhances primary IgG antibody responses to novel antigens. Further, mice rendered deficient in TRPV1- expressing nociceptors fail to develop primary IgG antibody responses to keyhole limpet hemocyanin or haptenated antigen.
CONCLUSIONS: This functional and genetic evidence indicates a critical role for nociceptor TRPV1 in antigen-specific primary antibody responses to novel antigens. These results also support consideration of potential therapeutic manipulation of nociceptor pathways using bioelectronic devices to enhance immune responses to foreign antigens.
METHODS: To understand the role of transient receptor potential vanilloid 1 (TRPV1)-expressing neurons in IgG responses, we generated TRPV1-Cre/Rosa-ChannelRhodopsin2 mice for precise optogenetic activation of TRPV1 + neurons and TRPV1-Cre/Lox-diphtheria toxin A mice for targeted ablation of TRPV1-expressing neurons. Antigen-specific antibody responses were longitudinally monitored for 28 days.
RESULTS: Here we show that TRPV1 expressing neurons are required to develop an antigen-specific immune response. We demonstrate that selective optogenetic stimulation of TRPV1+ nociceptors during immunization significantly enhances primary IgG antibody responses to novel antigens. Further, mice rendered deficient in TRPV1- expressing nociceptors fail to develop primary IgG antibody responses to keyhole limpet hemocyanin or haptenated antigen.
CONCLUSIONS: This functional and genetic evidence indicates a critical role for nociceptor TRPV1 in antigen-specific primary antibody responses to novel antigens. These results also support consideration of potential therapeutic manipulation of nociceptor pathways using bioelectronic devices to enhance immune responses to foreign antigens.
摘要：
背景：生物电子医学领域发展的关键是确定神经调节免疫功能的新途径。感觉神经元(称为伤害感受器)识别有害刺激并通过引发疼痛和防御行为来启动保护性反应。伤害感受器还与免疫细胞相互作用以调节宿主防御和炎症反应。然而,目前尚不清楚伤害感受器是否参与调节针对新抗原的初次IgG抗体应答.
方法：为了了解瞬时受体电位香草酸1（TRPV1）表达神经元在IgG反应中的作用，我们产生了TRPV1-Cre/Rosa-ChannelRhodopsin2小鼠,用于TRPV1+神经元的精确光遗传学激活;产生了TRPV1-Cre/Lox-白喉毒素A小鼠,用于靶向消融表达TRPV1的神经元.纵向监测抗原特异性抗体应答28天。
结果：在这里，我们表明表达TRPV1的神经元是产生抗原特异性免疫应答所必需的。我们证明，在免疫过程中TRPV1+伤害感受器的选择性光遗传学刺激显着增强了对新抗原的初次IgG抗体应答。Further,缺乏表达TRPV1的伤害感受器的小鼠未能产生针对匙孔血蓝蛋白或半抗原的初次IgG抗体应答。
结论：这一功能和遗传证据表明，伤害感受器TRPV1在针对新型抗原的抗原特异性初级抗体应答中具有关键作用。这些结果还支持考虑使用生物电子装置增强对外来抗原的免疫应答的伤害性感受器途径的潜在治疗操作。
方法：为了了解瞬时受体电位香草酸1（TRPV1）表达神经元在IgG反应中的作用，我们产生了TRPV1-Cre/Rosa-ChannelRhodopsin2小鼠,用于TRPV1+神经元的精确光遗传学激活;产生了TRPV1-Cre/Lox-白喉毒素A小鼠,用于靶向消融表达TRPV1的神经元.纵向监测抗原特异性抗体应答28天。
结果：在这里，我们表明表达TRPV1的神经元是产生抗原特异性免疫应答所必需的。我们证明，在免疫过程中TRPV1+伤害感受器的选择性光遗传学刺激显着增强了对新抗原的初次IgG抗体应答。Further,缺乏表达TRPV1的伤害感受器的小鼠未能产生针对匙孔血蓝蛋白或半抗原的初次IgG抗体应答。
结论：这一功能和遗传证据表明，伤害感受器TRPV1在针对新型抗原的抗原特异性初级抗体应答中具有关键作用。这些结果还支持考虑使用生物电子装置增强对外来抗原的免疫应答的伤害性感受器途径的潜在治疗操作。
