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checkpoints in the transcriptional control and signaling network that trigger either pro-inflammatory or
anti-inflammatory polarization.

There are known factors that can mediate early “predifferentiation” of monocytes towards either
inflammatory or anti-inflammatory phenotype in further differentiation to macrophages. However, it is
still disputed whether monocytes can be presented in the “pre-inflammatory” or “pre-anti-inflammatory”
state. In mice, it is likely that monocytes are generated as a Lyc6C-positive population in a bone marrow
that is focused on the “classical” inflammatory differentiation to macrophages. The loss of this marker can
designate the subset of blood monocytes that can survive in the bone marrow but develop expression of
higher Lyc6C surface expression to patrol the circulation in order to observe the endothelial integrity in
steady-state in response to inflammation. In humans, it is difficult to examine these modifications due to the
mature state of monocytes coming from the bone marrow to the circulation.

DECLARATIONS
Authors’ contributions
Text preparation: Orekhov AN
Collection and primary analysis of sources: Orekhova VA, Nikiforov NG, Myasoedova VA
In-depth analysis: Grechko AV, Romanenko EB, Zhang D
Writing the manuscript, editing English: Chistiakov DA

Availability of data and materials
Not applicable.

Financial support and sponsorship
This work was supported by Russian Science Foundation (18-15-00254), Russian Federation.

Conflicts of interest
All authors declared that there are no conflicts of interest.

Ethical approval and consent to participate
Not applicable.

Consent for publication
Not applicable.

Copyright
© The Author(s) 2019.

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