Research ArticleImmunology

Desynchronization of the molecular clock contributes to the heterogeneity of the inflammatory response

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Science Signaling  05 Mar 2019:
Vol. 12, Issue 571, eaau1851
DOI: 10.1126/scisignal.aau1851

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Desynchronized macrophage responses

Within a population of cells that are genetically and developmentally identical, individual cells do not necessarily respond identically to the same stimulus. Such differences may be due to cell-intrinsic variables, extracellular factors, or stochastic events. Allen et al. found that the proportion of macrophages within a population that produced the cytokine IL-12p40 in response to an inflammatory stimulus depended on the phase of the circadian clock (a cell-intrinsic factor) and the relative expression of clock genes. Although the central body clock resets the clock in peripheral tissues daily, the clocks of individual cells within a population gradually become desynchronized. These findings demonstrate that such differences in clock phase between individual macrophages contribute to the heterogeneity in their response to inflammatory stimuli.