Deltex1 is a target of the transcription factor NFAT that promotes T cell anergy.
The molecular process underlying T cell anergy is incompletely understood. Deltex1 (DTX1) is a Notch target with unknown physiological function. Here we show that Dtx1 was a transcription target of nuclear factor of activated T cells (NFAT) and participated in T cell anergy. DTX1 protein was upregulated during T cell anergy, and transgenic expression of Dtx1 attenuated T cell activation. DTX1 inhibited T cell activation by both E3-dependent and E3-independent mechanisms. In addition, DTX1 suppressed T cell activation in the absence of its Notch-binding domain. Importantly, DTX1 regulated the expression of two anergy-associated molecules, growth arrest and DNA-damage-inducible 45 beta (Gadd45 beta) and Cbl-b. DTX1 interacted with early growth response 2 (Egr-2) for optimum expression of Cbl-b. Furthermore, deficiency of DTX1 augmented T cell activation, conferred resistance to anergy induction, enhanced autoantibody generation, and increased inflammation. DTX1 therefore represents a component downstream of calcium-NFAT signaling that regulates T cell anergy.
Hsiao
Huey-Wen
HW
Graduate Institute of Microbiology and Immunology, National Yang-Ming University, Taipei 11221, Taiwan, ROC.
Liu
Wen-Hsien
WH
Wang
Chen-Jhe
CJ
Lo
Yu-Hsun
YH
Wu
Yung-Hsuan
YH
Jiang
Si-Tse
ST
Lai
Ming-Zong
MZ
D048868:Adaptor Proteins, Signal Transducing / Q000276:immunology / Q000378:metabolism; D000818:Animals; D000943:Antigens, Differentiation / Q000276:immunology / Q000378:metabolism; D015551:Autoimmunity / Q000276:immunology; D017635:Clonal Anergy / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000276:immunology; D051767:Early Growth Response Protein 2 / Q000276:immunology / Q000378:metabolism; D017874:Immediate-Early Proteins / Q000276:immunology / Q000378:metabolism; D007249:Inflammation / Q000276:immunology / Q000378:metabolism; D008099:Liver / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D008168:Lung / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D008213:Lymphocyte Activation / Q000235:genetics / Q000276:immunology; D008565:Membrane Proteins / Q000276:immunology / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D050778:NFATC Transcription Factors / Q000378:metabolism*; D050721:Proto-Oncogene Proteins c-cbl / Q000276:immunology / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D044767:Ubiquitin-Protein Ligases; D015854:Up-Regulation / Q000276:immunology; D000097642:GADD45 Proteins
D048868:Adaptor Proteins, Signal Transducing; D000943:Antigens, Differentiation; D004268:DNA-Binding Proteins; D051767:Early Growth Response Protein 2; D017874:Immediate-Early Proteins; D008565:Membrane Proteins; D050778:NFATC Transcription Factors; D050721:Proto-Oncogene Proteins c-cbl; D044767:Ubiquitin-Protein Ligases; C118387:Cblb protein, mouse; C497327:Egr2 protein, mouse; C490125:Gadd45b protein, mouse; D000097642:GADD45 Proteins; C484408:Laptm5 protein, mouse; C104035:Dtx1 protein, mouse