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Nat Immunol. 2013 Feb;14(2):127-35. doi: 10.1038/ni.2507. Epub 2012 Dec 23.

An alternative NFAT-activation pathway mediated by IL-7 is critical for early thymocyte development.

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Department of Molecular Pathology, Institute of Pathology, University of Würzburg, Würzburg, Germany.


Interleukin 7 (IL-7) has a critical role in the development of early CD4(-)CD8(-) double-negative (DN) thymocytes. Although the transcription factor STAT5 is an important component of IL-7 signaling, differences in the phenotypes of mice deficient in STAT5, IL-7, IL-7 receptor alpha (IL-7rα) or the kinase Jak3 suggest the existence of STAT5-independent IL-7 signaling. Here we found that IL-7-Jak3 signals activated the transcription factor NFATc1 in DN thymocytes by phosphorylating Tyr371 in the regulatory region of NFATc1. This NFAT-activation pathway was critical for the survival and development of DN thymocytes, as deficiency in NFATc1 blocked thymocyte development at the DN1 stage, leading to T cell lymphopenia. In addition, our results demonstrated a cooperative function for NFATc1 and STAT5 in guiding thymocyte development in response to IL-7 signals.

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