Pineal Regulation: Neuroendocrine immune relationship

松果体FceRIalpha：这一激动人心的发展始于微阵列的发现（J Biol Chem.2007 Nov 9;282（45）：32758-64）。 这表明，除了在夜间表达增加的许多基因之外，还有编码高亲和力IgE（FceRI）受体的α亚基的基因，其特征在于介导IgE介导的过敏反应，并在通过抗原/IgE复合物控制肥大细胞活化中发挥核心作用。 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报道，并且在该组织中高表达的发现在报道松果体影响免疫系统的背景下是令人感兴趣的，并且通过这种相互作用可能广泛地影响免疫功能，包括自身免疫性疾病、对病原体的免疫应答和对癌细胞的免疫应答。 这是与其他NIH研究人员和校外科学家合作研究的，试图更好地了解该基因的表达和IgE受体在松果体中的功能作用。 如上所述，发现FceRI α和FceRI γ多肽在松果体细胞（松果腺的褪黑激素分泌细胞）中表达。此外，Fcer 1a mRNA水平在夜间增加100倍，达到高于其他组织的水平。松果体FcepsilonRI α蛋白在夜间也从几乎检测不到的日间水平显著增加。我们的研究表明，松果体Fcer 1a mRNA水平的控制由一个良好的描述控制松果体功能的神经通路，这条通路包括主昼夜节律振荡器在视交叉上核，并通过中央和外周结构。松果体中FceRIalpha的昼夜节律表达由该神经回路通过肾上腺素能/环AMP机制驱动。发现FceRIa在松果体中的表达高于除大鼠嗜碱性白血病细胞系外检查的所有组织，使得松果体成为用于该受体生物学的未来研究的有价值的模型。 松果体FceRIalpha和FceRIgamma可能代表了神经内分泌和免疫系统之间以前未实现的分子联系。 松果体血管周围空间的吞噬细胞：“已知大鼠松果体血管周围空间含有对白细胞抗原具有免疫反应性的吞噬细胞，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。我们研究了这种细胞类型在小鼠的松果体。静脉注射辣根过氧化物酶后，在小鼠松果体毛细血管周围隙中发现具有明显溶酶体系统的吞噬细胞。细胞还表现出强酸性磷酸酶活性。血管周围细胞免疫阳性的MHC II类蛋白和CD 68，单核细胞/吞噬细胞的标志物。本研究证实小鼠松果体中存在具有抗原提呈特性的血管周围吞噬细胞。“来自国际时间生物学。23：393-401。

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.