Pineal Regulation: Neuroendocrine immune relationship

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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.