title: Thyrotropin acts as a T-cell developmental factor in mice and humans.
abstract: Using gene expression profiling, we detected differential thyrotropin receptor (TSH-R) expression during human T-cell development in the thymus. This expression pattern indicated a potential role for the TSH-R within the thymus, independent of its function in the thyroid gland. Here, we demonstrate that TSH-R expression is thymus-specific within the immune system. TSH was able to bind and activate the TSH-R present on thymocytes, thereby activating calcium signaling and cyclic adenosine monophosphate signaling pathways. Mice lacking functional TSH-R expression (hyt/hyt mice) were shown to have lower frequencies of DP and SP thymocytes compared to their heterozygous littermates. Moreover, addition of TSH to co-cultures of human thymocytes enhanced T-cell development. Thus, TSH acts as a previously unrecognized growth factor for developing T cells, with potential clinical use to enhance thymic output and thereby the functional T-cell repertoire in the periphery. The direct effects of TSH on thymocytes may also explain the thus far enigmatic thymic hyperplasia in Graves' disease.
authors.affiliation: 1 Department of Immunology, Erasmus University Medical Center , Rotterdam, The Netherlands .
authors.forename: Kim
authors.initials: K
authors.lastname: van der Weerd
authors.forename: P Martin
authors.initials: PM
authors.lastname: van Hagen
authors.forename: Benjamin
authors.initials: B
authors.lastname: Schrijver
authors.forename: Sjanneke J W M
authors.initials: SJ
authors.lastname: Heuvelmans
authors.forename: Leo J
authors.initials: LJ
authors.lastname: Hofland
authors.forename: Sigrid M A
authors.initials: SM
authors.lastname: Swagemakers
authors.forename: Ad J J C
authors.initials: AJ
authors.lastname: Bogers
authors.forename: Willem A
authors.initials: WA
authors.lastname: Dik
authors.forename: Theo J
authors.initials: TJ
authors.lastname: Visser
authors.forename: Jacques J M
authors.initials: JJ
authors.lastname: van Dongen
authors.forename: Aart-Jan
authors.initials: AJ
authors.lastname: van der Lelij
authors.forename: Frank J T
authors.initials: FJ
authors.lastname: Staal
mesh_terms: D000818:Animals; D002460:Cell Line; D002648:Child; D002675:Child, Preschool; D018920:Coculture Techniques; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D036341:Intercellular Signaling Peptides and Proteins / Q000502:physiology; D008807:Mice, Inbred BALB C; D011989:Receptors, Thyrotropin / Q000096:biosynthesis / Q000378:metabolism; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000502:physiology*; D013950:Thymus Gland / Q000378:metabolism*; D013972:Thyrotropin / Q000494:pharmacology / Q000502:physiology*
chemical_list: D036341:Intercellular Signaling Peptides and Proteins; D011989:Receptors, Thyrotropin; D013972:Thyrotropin