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

Publisher: Nature America Inc Country of Publication: United States NLM ID: 100941354 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1529-2916 (Electronic) Linking ISSN: 15292908 NLM ISO Abbreviation: Nat Immunol Subsets: MEDLINE

Original Publication: New York, NY : Nature America Inc. c2000-

Interleukin-7/*genetics ; NFATC Transcription Factors/*genetics ; STAT5 Transcription Factor/*genetics ; Signal Transduction/*immunology ; Thymocytes/*cytology; Animals ; CD4 Antigens/genetics ; CD4 Antigens/immunology ; CD8 Antigens/genetics ; CD8 Antigens/immunology ; Cell Differentiation ; Gene Expression Regulation ; Interleukin-7/immunology ; Janus Kinase 3/genetics ; Janus Kinase 3/immunology ; Lymphopenia/immunology ; Lymphopenia/pathology ; Mice ; Mice, Transgenic ; NFATC Transcription Factors/deficiency ; Phosphorylation ; Promoter Regions, Genetic ; Receptors, Interleukin-7/genetics ; Receptors, Interleukin-7/immunology ; STAT5 Transcription Factor/immunology ; Thymocytes/immunology ; Transcription, Genetic

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.

Comment in: Nat Immunol. 2013 Feb;14(2):116-7. doi: 10.1038/ni.2522. (PMID: 23334826)

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0 (CD4 Antigens)
0 (CD8 Antigens)
0 (Interleukin-7)
0 (NFATC Transcription Factors)
0 (Nfatc1 protein, mouse)
0 (Receptors, Interleukin-7)
0 (STAT5 Transcription Factor)
0 (interleukin-7, mouse)
EC 2.7.10.2 (Jak3 protein, mouse)
EC 2.7.10.2 (Janus Kinase 3)

Date Created: 20121225 Date Completed: 20130307 Latest Revision: 20211021

20250114

10.1038/ni.2507

23263556