Allen NC, Philip NH, Hui L, Zhou X, Franklin RA, Kong Y, Medzhitov R. 2019. Desynchronization of the molecular clock contributes to the heterogeneity of the inflammatory response. Science signaling. 12(571). Pubmed: 30837303 DOI:10.1126/scisignal.aau1851


Heterogeneity in the behavior of genetically and developmentally equivalent cells is becoming increasingly appreciated. There are several sources of cellular heterogeneity, including both intrinsic and extrinsic noise. We found that some aspects of heterogeneity in the response of macrophages to bacterial lipopolysaccharide (LPS) were due to intercellular desynchronization of the molecular clock, a cell-intrinsic oscillator. We found that the ratio of the relative expression of two clock genes, and , expressed in opposite phases of the clock, determined the fraction of cells that produced the cytokine IL-12p40 in response to LPS. The clock can be entrained by various environmental stimuli, making it a mechanism by which population-level heterogeneity and the inflammatory response can be regulated.
Copyright © 2019 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.

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Ruth Franklin’s laboratory explores the role of the innate immune system in tissue repair and homeostasis, with a focus on the communication between macrophages and non-immune cells within tissues.

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