Thyrotropin Acts as a T-Cell Developmental Factor in Mice and Humans

Kim Weerd, P.M. van Hagen, Benjamin Schrijver, SJWM Heuvelmans, Leo Hofland, Sigrid Swagemakers, Ad Bogers, Wim Dik, Theo Visser, Jacques Dongen, Aart Jan Lelij, Frank Staal

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23 Citations (Scopus)

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.
Original languageUndefined/Unknown
Pages (from-to)1051-1061
Number of pages11
JournalThyroid
Volume24
Issue number6
DOIs
Publication statusPublished - 2014

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