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

doi:10.1038/ni.1766

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 journal › Article › peer-review

103 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 CD62L^loCD44^hi 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 language	English (US)
Pages (from-to)	848-856
Number of pages	9
Journal	Nature Immunology
Volume	10
Issue number	8
DOIs	https://doi.org/10.1038/ni.1766
State	Published - 2009
Externally published	Yes

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

Fu, G, Vallée, S, Rybakin, V, McGuire, MV, Ampudia, J, Brockmeyer, C, Salek, M, Fallen, PR, Hoerter, JAH, Munshi, A, Huang, YH, Hu, J, Fox, HS, Sauer, K, Acuto, O & Gascoigne, NRJ 2009, 'Themis controls thymocyte selection through regulation of T cell antigen receptor-mediated signaling', Nature Immunology, vol. 10, no. 8, pp. 848-856. https://doi.org/10.1038/ni.1766

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title = "Themis controls thymocyte selection through regulation of T cell antigen receptor-mediated signaling",

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.",

author = "Guo Fu and S{\'e}bastien Vall{\'e}e and Vasily Rybakin and McGuire, {Marielena V.} and Jeanette Ampudia and Claudia Brockmeyer and Mogjiborahman Salek and Fallen, {Paul R.} and Hoerter, {John A.H.} and Anil Munshi and Huang, {Yina H.} and Jianfang Hu and Fox, {Howard S.} and Karsten Sauer and Oreste Acuto and Gascoigne, {Nicholas R.J.}",

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AU - Brockmeyer, Claudia

AU - Salek, Mogjiborahman

AU - Fallen, Paul R.

AU - Hoerter, John A.H.

AU - Munshi, Anil

AU - Huang, Yina H.

AU - Hu, Jianfang

AU - Fox, Howard S.

AU - Sauer, Karsten

AU - Acuto, Oreste

AU - Gascoigne, Nicholas R.J.

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

Abstract

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