<span class="word">Integrated <span class="word"><span class="changedDisabled">Functional <span class="word">and <span class="word">scRNA-<span class="word">Seq <span class="word"><span class="changedDisabled">Analyses <span class="word"><span class="changedDisabled">Reveal <span class="word"><span class="changedDisabled">Convergence <span class="word">of <span class="word">M-<span class="word allCaps">CSF– <span class="word">and <span class="word allCaps">GM-<span class="word allCaps">CSF–<span class="word"><span class="changedDisabled">Derived <span class="word"><span class="changedDisabled">Macrophages <span class="word"><span class="changedDisabled">Following <span class="word allCaps">IL-<span class="word">27 <span class="word"><span class="changedDisabled">Polarization

Macrophages differentiated with macrophage colony-stimulating factor (M-CSF) (M-Mac) are widely used as an experimental model. Interleukin 27 (IL-27)-polarized M-Mac (27M-Mac) suppress HIV replication; however, the effects of IL-27 polarization on granulocyte-macrophage colony-stimulating factor (GM-CSF)-induced macrophages (GM-Mac) remain less investigation. Here, we compare multiple functional properties and gene expression profiles of 27M-Mac and IL-27-polarized GM-Mac (27GM-Mac). M-Mac and GM-Mac were generated from monocytes of healthy donors and subsequently treated with IL-27 for three-day. HIV replication in 27M-Mac, GM-Mac, and 27GM-Mac was suppressed to nearly 10 % of that in M-Mac; however, single-cell RNA sequencing showed that M-Mac clustered with GM-Mac, and 27M-Mac clustered with 27GM-Mac. Expression of CD38 and secretion of CXCL9 and C1q were significantly increased in 27M-Mac and 27GM-Mac compared with M-Mac and GM-Mac. Although CD16 and CD64 expression increased in 27M-Mac and 27GM-Mac relative to their respective controls, phagocytic activity in 27M-Mac and 27GM-Mac was 30% of that in M-Mac. Autophagy was induced 3.7-fold more strongly in 27M-Mac than in M-Mac, reaching levels comparable to those in GM-Mac and 27GM-Mac. Collectively, these findings indicate that IL-27 polarizes M-Mac and GM-Mac toward transcriptionally and functionally similar subtypes, providing insight into the role of IL-27 in macrophage polarization and plasticity.