S. Chakarov et al., Science 363, eaau0964 (2019). DOI: 10.1126/science.aau0964
Macrophages are a heterogeneous cell population involved in tissue homeostasis, inflammation, and various pathologies. Although the major tissue-resident macrophage populations have been extensively studied, interstitial macrophages (IMs) residing within the tissue parenchyma remain poorly defined. Here we studied IMs from murine lung, fat, heart, and dermis. We identified two independent IM subpopulations that are conserved across tissues: Lyve1loMHCIIhiCX3CR1hi (Lyve1loMHCIIhi) and Lyve1hiMHCIIloCX3CR1lo (Lyve1hiMHCIIlo) monocyte-derived IMs, with distinct gene expression profiles, phenotypes, functions, and localizations. Using a new mouse model of inducible macrophage depletion (Slco2b1flox/DTR), we found that the absence of Lyve1hiMHCIIlo IMs exacerbated experimental lung fibrosis. Thus, we demonstrate that two independent populations of IMs coexist across tissues and exhibit conserved niche-dependent functional programming.
The CyTOF, bioinformatics, and immunogenomics platforms are part of the SIgN Immunomonitoring platform (supported by a BMRC IAF 311006 grant and BMRC transition funds #H16/99/b0/011). This work was supported by EMBO YIP, Singapore Immunology Network core funding, Agency for Science, Technology and Research (A*STAR), and Singapore NRF Senior Investigatorship (NRFI2017-02) to F.G.; AXA Research Fund (F.G. and B.Mali.); and NMRC (CBRGnov094) and NRF grants to V.A. A.S. is funded by an Emmy Noether fellowship (SCHL 2116/1-1) of the German Research Foundation and a Young Investigator Award of the Biomedical Research Council Singapore.
The full paper can be downloaded from the publisher's URL: https://doi.org/10.1126/science.aau0964