title: Immunological regulation of metabolism--a novel quintessential role for the immune system in health and disease.
abstract: The hypothalamus-pituitary-thyroid (HPT) axis is an integrated hormone network that is essential for maintaining metabolic homeostasis. It has long been known that thyroid stimulating hormone (TSH), a central component of the HPT axis, can be made by cells of the immune system; however, the role of immune system TSH remains enigmatic and most studies have viewed it as a cytokine used to regulate immune function. Recent studies now indicate that immune system-derived TSH, in particular, a splice variant of TSHβ that is preferentially made by cells of the immune system, is produced by a subset of hematopoietic cells that traffic to the thyroid. On the basis of these and other findings, we propose the novel hypothesis that the immune system is an active participant in the regulation of basal metabolism. We further speculate that this process plays a critical role during acute and chronic infections and that it contributes to a wide range of chronic inflammatory conditions with links to thyroid dysregulation. This hypothesis, which is amenable to empirical analysis, defines a previously unknown role for the immune system in health and disease, and it provides a dynamic connection between immune-endocrine interactions at the organismic level.
authors.affiliation: Department of Diagnostic Sciences, Dental Branch, University of Texas Health Science Center at Houston, Houston, TX 77054, USA.
authors.forename: Jeremy S
authors.initials: JS
authors.lastname: Schaefer
authors.forename: John R
authors.initials: JR
authors.lastname: Klein
mesh_terms: D017398:Alternative Splicing; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002908:Chronic Disease; D006801:Humans; D007030:Hypothalamo-Hypophyseal System / Q000276:immunology / Q000378:metabolism; D007107:Immune System / Q000378:metabolism*; D007239:Infections / Q000276:immunology / Q000378:metabolism; D007249:Inflammation / Q000276:immunology* / Q000378:metabolism; D007962:Leukocytes / Q000378:metabolism*; D018448:Models, Immunological; D008969:Molecular Sequence Data; D020033:Protein Isoforms / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D012689:Sequence Homology, Nucleic Acid; D013961:Thyroid Gland / Q000276:immunology / Q000378:metabolism; D013972:Thyrotropin / Q000235:genetics / Q000378:metabolism*; D037322:Thyrotropin, beta Subunit / Q000235:genetics / Q000378:metabolism
chemical_list: D020033:Protein Isoforms; D037322:Thyrotropin, beta Subunit; D013972:Thyrotropin
references.citation: J Immunol. 1989 Feb 1;142(3):744-7
references.pmid: 2492328
references.citation: Clin Rheumatol. 2007 Nov;26(11):1891-4
references.pmid: 17372671
references.citation: J Immunol. 1986 Jul 1;137(1):197-200
references.pmid: 3086448
references.citation: Clin Geriatr Med. 1992 Feb;8(1):19-34
references.pmid: 1576576
references.citation: Ann N Y Acad Sci. 2002 Jun;966:496-501
references.pmid: 12114310
references.citation: Thyroid. 2002 Dec;12(12):1147-8
references.pmid: 12593730
references.citation: Thyroidology. 1992 Apr;4(1):45-8
references.pmid: 1284333
references.citation: Endocrinology. 2009 May;150(5):2237-43
references.pmid: 19095738
references.citation: Liver Int. 2009 Aug;29(7):1094-100
references.pmid: 19291181
references.citation: Gen Comp Endocrinol. 2009 Jul;162(3):241-4
references.pmid: 19364510
references.citation: Thyroid. 2001 Oct;11(10):981-8
references.pmid: 11716048
references.citation: J Allergy Clin Immunol. 1999 Sep;104(3 Pt 1):595-600
references.pmid: 10482833
references.citation: Eur J Nucl Med Mol Imaging. 2002 Aug;29 Suppl 2:S417-24
references.pmid: 12192541
references.citation: Genes Immun. 2009 Jan;10(1):18-26
references.pmid: 18754015
references.citation: Immunol Lett. 2005 Jun 15;99(1):36-44
references.pmid: 15894109
references.citation: Obesity (Silver Spring). 2010 Apr;18(4):854-7
references.pmid: 19834461
references.citation: Mol Cell Endocrinol. 1989 Jul;64(2):229-41
references.pmid: 2507375
references.citation: Cell Immunol. 1999 Mar 15;192(2):159-66
references.pmid: 10087184
references.citation: Gynecol Endocrinol. 2007 Jun;23(6):332-7
references.pmid: 17616857
references.citation: Biochem Biophys Res Commun. 1984 Nov 30;125(1):30-4
references.pmid: 6508801
references.citation: Bone. 2010 Mar;46(3):747-51
references.pmid: 19892039
references.citation: Clin Exp Rheumatol. 2009 Jul-Aug;27(4 Suppl 55):S20-5
references.pmid: 19822041
references.citation: Ital J Gastroenterol. 1995 Jul-Aug;27(6):291-5
references.pmid: 8562993
references.citation: Mol Endocrinol. 1988 Feb;2(2):95-100
references.pmid: 3398850
references.citation: J Exp Biol. 2004 Jan;207(Pt 1):55-65
references.pmid: 14638833
references.citation: Blood. 2003 Jan 1;101(1):119-23
references.pmid: 12393601
references.citation: Acta Paediatr. 2007 Mar;96(3):406-9
references.pmid: 17407466
references.citation: J Cell Biochem. 2008 Sep 1;105(1):271-6
references.pmid: 18523983
references.citation: Proc Natl Acad Sci U S A. 1983 Oct;80(19):6010-3
references.pmid: 6351072
references.citation: Science. 1994 Sep 23;265(5180):1860-2
references.pmid: 8091211
references.citation: J Immunol. 2000 Jun 15;164(12):6158-65
references.pmid: 10843665
references.citation: Infect Immun. 2006 Mar;74(3):1883-9
references.pmid: 16495563
references.citation: Eur Respir J. 2009 Oct;34(4):975-96
references.pmid: 19797671
references.citation: Circ Shock. 1991 Nov;35(3):181-91
references.pmid: 1663842
references.citation: Science. 1997 Mar 28;275(5308):1937-9
references.pmid: 9072972
references.citation: J Clin Endocrinol Metab. 2010 Jan;95(1):430-8
references.pmid: 19897675
references.citation: Cell Immunol. 1995 Apr 1;161(2):299-302
references.pmid: 7697742
references.citation: Eur J Dermatol. 2009 May-Jun;19(3):221-3
references.pmid: 19251564
references.citation: J Autoimmun. 2009 Sep;33(2):121-4
references.pmid: 19419839
references.citation: J Biol Chem. 1997 Jun 13;272(24):15532-40
references.pmid: 9182589
references.citation: Cell Immunol. 2001 Sep 15;212(2):92-100
references.pmid: 11748925