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Restraint of inflammatory signaling by interdependent strata of negative regulatory pathways

Nature Immunology volume 13, pages 916–924 (2012)Cite this article

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Abstract

Activation of Toll-like receptor (TLR) signaling and related pathways by microbial products drives inflammatory responses, host-defense pathways and adaptive immunity. The cost of excessive inflammation is cell and tissue damage, an underlying cause of many acute and chronic diseases. Coincident with activation of TLR signaling, a plethora of anti-inflammatory pathways and mechanisms begin to modulate inflammation until tissue repair is complete. Whereas most studies have focused on the signaling components immediately downstream of the TLRs, this Review summarizes the different levels of anti-inflammatory pathways that have evolved to abate TLR signaling and how they are integrated to prevent cell and tissue destruction.

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Figure 1: Negative regulation of IL-1β production, signaling and bioavailability as an example of multitiered anti-inflammatory integration.
Figure 2: Three fundamental levels for transcriptional suppression of inflammation (stratum 5).
Figure 3: IL-10 regulates the production of downstream factors that control many strata of inflammation.

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Acknowledgements

We thank F. Kratochvill, P. Ward and G. Hajishengallis for comments. Supported by the US National Institutes of Health (R01 AI073868, R01 CA127279, R01 GM086372 and P30 CA21765), The Hartwell Foundation and The American Lebanese Syrian Associated Charities.

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  1. Department of Infectious Diseases and Department of Immunology, St. Jude Children's Research Hospital, Memphis, Tennessee, USA

    Peter J Murray

  2. Department of Microbiology, Immunology, and Molecular Genetics, University of California Los Angeles, Los Angeles, California, USA

    Stephen T Smale

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Murray, P., Smale, S. Restraint of inflammatory signaling by interdependent strata of negative regulatory pathways. Nat Immunol 13, 916–924 (2012). https://doi.org/10.1038/ni.2391

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