Themis controls thymocyte selection through regulation of T cell antigen receptor-mediated signaling

Guo Fu, Sébastien Vallée, Vasily Rybakin, Marielena V. McGuire, Jeanette Ampudia, Claudia Brockmeyer, Mogjiborahman Salek, Paul R. Fallen, John A.H. Hoerter, Anil Munshi, Yina H. Huang, Jianfang Hu, Howard S. Fox, Karsten Sauer, Oreste Acuto, Nicholas R.J. Gascoigne

Research output: Contribution to journalArticle

84 Scopus citations

Abstract

Themis (thymocyte-expressed molecule involved in selection), a member of a family of proteins with unknown functions, is highly conserved among vertebrates. Here we found that Themis had high expression in thymocytes between the pre-T cell antigen receptor (pre-TCR) and positive-selection checkpoints and low expression in mature T cells. Themis-deficient thymocytes showed defective positive selection, which resulted in fewer mature thymocytes. Negative selection was also impaired in Themis-deficient mice. A greater percentage of Themis-deficient T cells had CD4+CD25+Foxp3+ regulatory and CD62LloCD44hi memory phenotypes than did wild-type T cells. In support of the idea that Themis is involved in TCR signaling, this protein was phosphorylated quickly after TCR stimulation and was needed for optimal TCR-driven calcium mobilization and activation of the kinase Erk.

Original languageEnglish (US)
Pages (from-to)848-856
Number of pages9
JournalNature Immunology
Volume10
Issue number8
DOIs
StatePublished - 2009

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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    Fu, G., Vallée, S., Rybakin, V., McGuire, M. V., Ampudia, J., Brockmeyer, C., Salek, M., Fallen, P. R., Hoerter, J. A. H., Munshi, A., Huang, Y. H., Hu, J., Fox, H. S., Sauer, K., Acuto, O., & Gascoigne, N. R. J. (2009). Themis controls thymocyte selection through regulation of T cell antigen receptor-mediated signaling. Nature Immunology, 10(8), 848-856. https://doi.org/10.1038/ni.1766