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J. Biol. Chem., Vol. 282, Issue 45, 32758-32764, November 9, 2007

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Neural Adrenergic/Cyclic AMP Regulation of the Immunoglobulin E Receptor -Subunit Expression in the Mammalian Pinealocyte

A NEUROENDOCRINE/IMMUNE RESPONSE LINK?^*

Surajit Ganguly¹, Cristina Grodzki^¶, David Sugden^||, Morten Møller^**, Sandra Odom, Pascaline Gaildrat, Igal Gery, Reuben P. Siraganian^¶, Juan Rivera, and David C. Klein²

From the Section on Neuroendocrinology, Office of the Scientific Director, NICHD, National Institutes of Health, Bethesda, Maryland 20892, the Department of Pharmacology and Molecular Sciences, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, the ^¶Oral Infection and Immunity Branch, NIDCR, National Institutes of Health, Bethesda, Maryland 20892, the ^||Division of Reproduction and Endocrinology, School of Biomedical and Health Sciences, King's College London, London Bridge, London SE1 1UL, United Kingdom, the ^**Department of Neurobiology and Pharmacology, Panum Institute, University of Copenhagen, Copenhagen, Denmark, the Molecular Inflammation Section, Molecular Immunology and Inflammation Branch, NIAMS, National Institutes of Health, Bethesda, Maryland 20892, and the Laboratory of Immunology, NEI, National Institutes of Health, Bethesda, Maryland 20892

The high affinity immunoglobulin E receptor (FcRI) complex is dedicated to immunoglobulin E-mediated allergic responses. Expression of the FcRI receptor is thought to be relatively stable and limited to mast cells, basophils, eosinophils, monocytes, Langerhans cells, platelets, and neutrophils. We now report that the FcRI and FcRI polypeptides are expressed in the pinealocyte, the melatonin-secreting cell of the pineal gland. Moreover, Fcer1a mRNA levels increased 100-fold at night to levels that were higher than in other tissues examined. Pineal FcRI protein also increased 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 FcRI in the pineal gland is driven by this neural circuit via an adrenergic/cyclic AMP mechanism. Pineal FcRI and FcRI may represent a previously unrealized molecular link between the neuroendocrine and immune systems.

Received for publication, July 20, 2007 , and in revised form, August 17, 2007.

^* This study was supported by the Intramural Research Programs of NICHD (National Institutes of Health), NIAMS (National Institutes of Health), and NIDCR (National Institutes of Health), and the Lundbeck and Novo Nordisk Foundations. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

The on-line version of this article (available at http://www.jbc.org) contains supplemental data and supplemental Figs. 1–3.

¹ Current address: The Centre for Genomic Application, 254, Ground Floor, Phase-III Okhla Industrial Estate, New Delhi, India 110020.

² To whom correspondence should be addressed: Section on Neuroendocrinology, NICHD, National Institutes of Health, Bldg. 49, Rm. 6A82, Bethesda, MD 20892. Tel.: 301-496-6914; Fax: 301-480-3526; E-mail: kleind{at}mail.nih.gov.

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