TY - JOUR
T1 - Transcriptional mechanisms underlying lymphocyte tolerance
AU - Macián, Fernando
AU - García-Cózar, Francisco
AU - Im, Sin Hyeog
AU - Horton, Heidi F.
AU - Byrne, Michael C.
AU - Rao, Anjana
N1 - Funding Information:
We thank members of the Rao and Byrne laboratories for valuable discussions, K. Murphy for the original version of the retroviral vector, and G. Nolan for the Phoenix Ecotropic packaging cell line. This work was supported by National Institutes of Health grants CA42471 and AI48213 (to A.R.)
PY - 2002/6/14
Y1 - 2002/6/14
N2 - In lymphocytes, integration of Ca2+ and other signaling pathways results in productive activation, while unopposed Ca2+ signaling leads to tolerance or anergy. We show that the Ca2+-regulated transcription factor NFAT has an integral role in both aspects of lymphocyte function. Ca2+/calcineurin signaling induces a limited set of anergy-associated genes, distinct from genes induced in the productive immune response; these genes are upregulated in vivo in tolerant T cells and are largely NFAT dependent. T cells lacking NFAT1 are resistant to anergy induction; conversely, NFAT1 induces T cell anergy if prevented from interacting with its transcriptional partner AP-1 (Fos/Jun). Thus, in the absence of AP-1, NFAT imposes a genetic program of lymphocyte anergy that counters the program of productive activation mediated by the cooperative NFAT:AP-1 complex.
AB - In lymphocytes, integration of Ca2+ and other signaling pathways results in productive activation, while unopposed Ca2+ signaling leads to tolerance or anergy. We show that the Ca2+-regulated transcription factor NFAT has an integral role in both aspects of lymphocyte function. Ca2+/calcineurin signaling induces a limited set of anergy-associated genes, distinct from genes induced in the productive immune response; these genes are upregulated in vivo in tolerant T cells and are largely NFAT dependent. T cells lacking NFAT1 are resistant to anergy induction; conversely, NFAT1 induces T cell anergy if prevented from interacting with its transcriptional partner AP-1 (Fos/Jun). Thus, in the absence of AP-1, NFAT imposes a genetic program of lymphocyte anergy that counters the program of productive activation mediated by the cooperative NFAT:AP-1 complex.
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U2 - 10.1016/S0092-8674(02)00767-5
DO - 10.1016/S0092-8674(02)00767-5
M3 - Article
C2 - 12086671
AN - SCOPUS:0037077135
SN - 0092-8674
VL - 109
SP - 719
EP - 731
JO - Cell
JF - Cell
IS - 6
ER -