Pineal Regulation: Neuroendocrine immune relationship

松果体调节：神经内分泌免疫关系

• 批准号: 8149221
• 负责人: David Klein
• 金额: $ 7.66万
• 依托单位: EUNICE KENNEDY SHRIVER NATIONAL INSTITUTE OF CHILD HEALTH & HUMAN DEVELOPMENT
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/8149221
• 关键词: Acid Phosphatase; Adrenergic Agents; Affinity; Basophilic leukemia; Cyclic AMP; Development; Etiology; Exhibits; Extramural Activities; Future; Gene Expression; Genes; Goals; Graves' Disease; HLA Antigens; Histocompatibility Antigens Class II; Hormones; Horseradish Peroxidase; IgE; IgE Receptors; Immune; Immune system; Insulin-Dependent Diabetes Mellitus; International; Langerhans cell; Link; Literature; Melatonin; Microglia; Molecular; Multiple Sclerosis; Mus; Neural Pathways; Neurosecretory Systems; Pathway interactions; Peripheral; Pinealocyte; Regulation; Systemic Lupus Erythematosus; United States National Institutes of Health; base; eosinophil; immune function; intravenous injection; macrophage; mast cell; monocyte

Pineal FceRIalpha : This exciting development started with finding made by microarray (J Biol Chem. 2007 Nov 9;282(45):32758-64). This revealed that amoung the many genes that increase in expression at night, was the gene encoding the alpha subunit of the high affinity IgE (FceRI) receptor, which has been characterized as mediating IgE-mediated allergic responses and to play a central role in controlling Mast cell activation by the antigen/IgE complex. This gene is known to be expressed in mast cells, basophils, eosinophils, monocytes, Langerhans cells, platelets, and neutrophils. The expression of this gene in the pineal gland has not been reported and the finding of high expression in this tissue was of interest in the context of report that the pineal gland impacts the immune system and through this interaction might impact immune function broadly, including autoimmune disease, immune response to pathogens and the immune reponse to cancer cells. This was studied in collaboration with other NIH investigators and extramural scientists, in an attempt to better understand expression of this gene and the functional role IgE receptor plays in the pineal gland. As described, it was found that the FceRIalpha and FceRIgammapolypeptides are expressed in the pinealocyte, the melatonin secreting cell of the pineal gland. Moreover, Fcer1a mRNA levels increase 100-fold at night to levels that are higher than in other tissues examined. Pineal FcepsilonRIalpha protein also increases markedly at night from nearly undetectable daytime levels. Our studies indicate that pineal Fcer1a mRNA levels are controlled by a well-described neural pathway that controls pineal function; this pathway includes the master circadian oscillator in the suprachiasmatic nucleus and passes through central and peripheral structures. The circadian expression of FceRIalpha in the pineal gland is driven by this neural circuit via an adrenergic/cyclic AMP mechanism. Expression of FceRIa was found to be higher in the pineal gland than in all tissues examined except for a rat basophilic leukemia cell line, making the pineal gland a valuable model for future study of the biology of this receptor. Pineal FceRIalpha and FceRIgamma may represent a previously unrealized molecular link between the neuroendocrine and immune systems. Phagocytic cells in the pineal perifascular space: "The perivascular space of the rat pineal gland is known to contain phagocytic cells that are immunoreactive for leukocyte antigens, and thus they appear to belong to the macrophage/microglial cell line. These cells also contain MHC class II proteins. We investigated this cell type in the pineal gland of mice. Actively phagocytosing cells with a prominent lysosomal system were found in the pericapillary spaces of the mouse pineal gland following intravenous injection of horseradish peroxidase. The cells also exhibited strong acid phosphatase activity. Perivascular cells were immunopositive for MHC class II protein and for CD68, a marker of monocytes/phagocytes. This study verifies that perivascular phagocytes with antigen-presenting properties are present in the mouse pineal gland." From Chronobiology International. 23:393-401.

松果体FceRIpha：这一令人兴奋的发展始于微阵列(J Biol Chem.2007年11月9日；282(45)：32758-)。这表明，在夜间表达增加的众多基因中，编码高亲和力IgE(FceRI)受体α亚基的基因被认为是介导IgE介导的变态反应的基因，并在通过抗原/IgE复合体控制肥大细胞激活方面发挥核心作用。 已知该基因在肥大细胞、嗜碱性粒细胞、嗜酸性粒细胞、单核细胞、朗格汉斯细胞、血小板和中性粒细胞中表达。该基因在松果体中的表达尚未见报道，在松果体影响免疫系统并通过这种相互作用可能广泛影响免疫功能，包括自身免疫性疾病、对病原体的免疫反应和对癌细胞的免疫反应的背景下，该基因在松果体组织中的高表达引起了人们的兴趣。 这项研究是与其他NIH研究人员和校外科学家合作进行的，试图更好地了解该基因的表达以及IgE受体在松果体中所起的功能作用。 如上所述，研究发现FceRIpha和FceRIGammapoly多肽在松果体细胞中表达，松果体细胞是松果体的褪黑激素分泌细胞。此外，Fcer1a的mRNA水平在夜间增加100倍，达到高于所检测的其他组织的水平。松果体FcepsilonRIpha蛋白也从白天几乎检测不到的水平在夜间显著增加。我们的研究表明，松果体Fcer1a mRNA水平受一条控制松果体功能的神经通路控制，该通路包括视交叉上核中的主要昼夜节律振荡器，并通过中枢和外周结构。FceRIpha在松果体中的昼夜表达是由这一神经回路通过肾上腺素能/环化AMP机制驱动的。FceRIa在松果体中的表达高于除大鼠嗜碱性白血病细胞系外的所有组织，使松果体成为未来该受体生物学研究的有价值的模型。 松果体FceRIpha和FceRIGamma可能代表了神经内分泌和免疫系统之间以前未意识到的分子联系。 松果体血管周围间隙的吞噬细胞：“已知大鼠松果体的血管周围间隙含有对白细胞抗原免疫反应阳性的吞噬细胞，因此它们似乎属于巨噬细胞/小胶质细胞系。这些细胞还含有MHC II类蛋白。我们在小鼠的松果体中研究了这种细胞类型。静脉注射辣根过氧化物酶后，在小鼠松果体周围间隙发现具有明显溶酶体系统的活跃吞噬细胞。细胞也表现出很强的酸性磷酸酶活性。血管周围细胞MHC-II类蛋白和单核/巨噬细胞标志物CD68免疫阳性。这项研究证实了具有抗原呈递特性的血管周围吞噬细胞存在于小鼠松果体中。来自国际时间生物学协会。23：393-401。

项目成果

Muscleblind-like 2: circadian expression in the mammalian pineal gland is controlled by an adrenergic-cAMP mechanism.

Muscleblind-like 2：哺乳动物松果体中的昼夜节律表达受肾上腺素cAMP机制控制。

• DOI: 10.1111/j.1471-4159.2009.06184.x
• 发表时间: 2009
• 期刊: Journal of neurochemistry
• 影响因子: 4.7
• 作者: Kim,Jong-So;Coon,StevenL;Weller,JoanL;Blackshaw,Seth;Rath,MartinF;Møller,Morten;Klein,DavidC
• 通讯作者: Klein,DavidC