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A Distal Enhancer in Il12b Is the Target of Transcriptional Repression by the STAT3 Pathway and Requires the Basic Leucine Zipper (B-ZIP) Protein NFIL3

  1. Author:
    Smith, A. M.
    Qualls, J. E.
    O'Brien, K.
    Balouzian, L.
    Johnson, P. F.
    Schultz-Cherry, S.
    Smale, S. T.
    Murray, P. J.

  2. Author Address

    [Smith, AM; Qualls, JE; O'Brien, K; Balouzian, L; Schultz-Cherry, S; Murray, PJ] St Jude Childrens Hosp, Dept Infect Dis, Memphis, TN 38105 USA [Smith, AM; Qualls, JE; Balouzian, L; Murray, PJ] St Jude Childrens Hosp, Dept Immunol, Memphis, TN 38105 USA [Johnson, PF] NCI, Lab Canc Prevent, Ctr Canc Res, Ft Detrick, MD 21702 USA [Smale, ST] Univ Calif Los Angeles, Dept Microbiol Immunol & Mol Genet, Los Angeles, CA 90095 USA;Murray, PJ (reprint author), St Jude Childrens Hosp, Dept Infect Dis, Mail Stop 320,262 Danny Thomas Pl, Memphis, TN 38105 USA;peter.murray@stjude.org
    1. Year: 2011
    2. Date: Jul
  2. Journal: Journal of Biological Chemistry
    1. 286
    2. 26
    3. Pages: 23582-23590
  4. Type of Article: Article
  5. ISSN: 0021-9258
  1. Abstract:

    Deregulated IL-12 and IL-23 production from activated myeloid lineage cells is a key driver of numerous T cell-dependent autoimmune and inflammatory diseases. IL-12 and IL-23 share a common p40 subunit encoded by Il12b, which is negatively regulated at the transcriptional level by the STAT3(signal transducer and activator of transcription 3)-activating anti-inflammatory cytokine IL-10. We found that IL-10 targets an enhancer 10 kb upstream of the Il12b transcriptional start site. Within the enhancer, a single 10-bp site is required for the inhibitory effects of IL-10 and is bound by NFIL3 (nuclear factor, interleukin 3-regulated), a B-ZIP transcription factor. Myeloid cells lacking NFIL3 produce excessive IL-12p40 and increased IL-12p70. Thus, the STAT3-dependent expression of NFIL3 is a key component of a negative feedback pathway in myeloid cells that suppresses proinflammatory responses.

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External Sources

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  2. DOI: 10.1074/jbc.M111.249235
  3. View record in Web of Science®
  4. WOS: 000292025000088

Library Notes

  1. Fiscal Year: FY2010-2011
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