Transcriptional mechanisms underlying lymphocyte tolerance

Fernando Macián, Francisco García-Cózar, Sin Hyeog Im, Heidi F. Horton, Michael C. Byrne, Anjana Rao

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Abstract

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.

Original languageEnglish (US)
Pages (from-to)719-731
Number of pages13
JournalCell
Volume109
Issue number6
DOIs
StatePublished - Jun 14 2002
Externally publishedYes

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ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Macián, F., García-Cózar, F., Im, S. H., Horton, H. F., Byrne, M. C., & Rao, A. (2002). Transcriptional mechanisms underlying lymphocyte tolerance. Cell, 109(6), 719-731. https://doi.org/10.1016/S0092-8674(02)00767-5