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Transcription Factors That Regulate Macrophage Development and Function

  • Chapter
The Macrophage as Therapeutic Target

Part of the book series: Handbook of Experimental Pharmacology ((HEP,volume 158))

Abstract

The transcription factors that play a major role in the development and function of the monocyte/macrophage lineage are outlined in this review. Hematopoiesis proceeds through the binding of specific combinations of transcription factors leading to a temporal and lineage-restricted pattern of gene expression. We summarize current knowledge of how transcription factors are able to drive monocyte differentiation from early pluripotent progenitors. These transcription factors include numerous homeobox family proteins, AML-1, Pu.1, MZF-1, Egr-1, ICSBP, and STAT family proteins. The transcription factors that control inducible gene expression in mature macrophages are also covered. Macrophages are able to respond to a range of bacterial products and play a critical role in both the innate and adaptive immune response to infection. The inducible transcription factors that regulate inflammatory and anti-microbial gene products covered here include NF-κB/Rel, IRF, STAT, and C/EBP family proteins. This activation of macrophages must be precisely regulated to prevent damage to host tissue. Many transcription factors can act as repressors of gene expression in macrophages and the signals that down-regulate inflammatory responses such as activation of TGFβ, PPARγ and glucocorticoid receptors are discussed. Macrophages play a fundamental role in adaptive immunity and are likely to influence the formation of either a Th1 or Th2 pattern of immune reactivity. We briefly review the current understanding of how activation of different transcription factors can influence the profile of cytokines expressed in macrophages and contribute to the formation of distinct immune responses.

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  1. Department of Microbiology, University of Queensland, Molecular Bioscience Building, Q4072, Australia

    D. A. Hume & S. R. Himes

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    Siamon Gordon

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Hume, D.A., Himes, S.R. (2003). Transcription Factors That Regulate Macrophage Development and Function. In: Gordon, S. (eds) The Macrophage as Therapeutic Target. Handbook of Experimental Pharmacology, vol 158. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-55742-2_2

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