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fcerialpha：这种令人兴奋的发展始于微阵列的发现（J BiolChem。200711月9日； 282（45）：32758-64）。 这表明，夜间表达增加的许多基因是编码高亲和力IgE（FCERI）受体的α亚基的基因，该基因的特征是介导IgE介导的IgE介导的过敏反应，并在控制抗原/IgE复合物控制肥大细胞激活中起着核心作用。 已知该基因在肥大细胞，嗜碱性粒细胞，单核细胞，Langerhans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报道，在报告中，在该组织中高表达的发现是在报告的背景下，松果体会影响免疫系统，并且通过这种相互作用可能会广泛影响免疫功能，包括自身免疫性疾病，免疫反应，对病原体和对癌细胞的免疫反应。 这是与其他NIH研究者和壁外科学家合作的研究，以便更好地了解该基因的表达以及IgE受体在松果体中发挥的功能作用。 如上所述，发现fcerialpha和fcerigammapolypoptides在松果体（松果体的褪黑激素分泌细胞）中表达。此外，夜间FCER1A mRNA水平增加了100倍，高于所检查的其他组织的水平。松果体fcepsilonrialpha蛋白在夜间从几乎无法检测到的白天水平也明显增加。我们的研究表明，松果体FCER1A mRNA水平受到控制松果体功能的良好描述的神经途径的控制。该途径包括上核中的昼夜节律振荡器，并通过中央和外围结构。松果体中Fcerialpha的昼夜节律表达是由该神经回路通过肾上腺素/环状AMP机制驱动的。在松果体中发现FCERIA的表达高于所检查的所有组织，除了大鼠嗜碱性白血病细胞系，使松果体成为对该受体生物学的未来研究的宝贵模型。 松果体fcerialpha和fcerigamma可能代表神经内分泌和免疫系统之间先前未实现的分子联系。 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在静脉注射辣根过氧化物酶后，在小鼠松果体的周围空间中发现了突出的溶酶体系统。小鼠松果体中存在抗原呈递特性。”来自Chronobiology International。 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