Editors' ChoiceInflammation

Behold morphing monocytes at sites of liver damage

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Science Translational Medicine  29 Apr 2015:
Vol. 7, Issue 285, pp. 285ec70
DOI: 10.1126/scitranslmed.aab3136

The inflammatory response to tissue damage has a duplicitous nature. How inflammation can have both positive and negative effects on tissue repair was revealed by the identification of distinct subsets of macrophages—with a classical proinflammatory phenotype at one end of the spectrum and with a pro-repair phenotype at the other. Nevertheless, there are still gaps in our understanding of the origin of these distinct cell types, their plasticity, and mechanisms of polarization.

To visualize the temporal dynamics of the monocyte/macrophage response to sterile liver damage produced by heat, Dal-Secco et al. performed impressive intravital imaging of mice carrying red or green fluorescently labeled monocytes, with the two colors representing the two ends of the inflammatory spectrum. Soon after injury, monocytes with classic proinflammatory features were recruited from the local vasculature to encircle the site of damage. Dal-Secco et al. then observed the transitioning of these cells, in situ, in real-time, from a proinflammatory to a pro-repair phenotype, revealing that these cells can have intermediate phenotypes and clarifying the source of the pro-repair monocytes. This change in phenotype was accompanied by modifications in cell function, with the pro-repair monocytes contributing to debris clearance and matrix production. Whether this result pertains to other tissues with different resident monocyte populations or tissues suffering more significant damage or infection are important future questions.

The authors also found that the cell surface chemokine receptor CCR2 mediated the initial monocyte recruitment to the site of tissue damage, and the cooperative action of the cytokines interleukin-4 (IL-4) and IL-10 drove the transition from one cellular phenotype to the other. These regulatory molecules are exciting targets that could allow strategic steering of macrophages to express desirable features in the right place at the right time—for therapeutic benefit. Such manipulation of inflammation would be of value in the treatment of inflammation-associated diseases, not only in scenarios of tissue damage.

D. Dal-Secco et al., A dynamic spectrum of monocytes arising from the in situ reprogramming of CCR2+ monocytes at a site of sterile injury. J. Exp. Med. 212, 447–456 (2015). [Abstract]

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