Tissue-specific signals control reversible program of localization and functional polarization of macrophages.

By Y. Okabe, R. Medzhitov. 2014

836 citations recorded by the source corpus.

SUMMARY Tissue-resident macrophages are highly heterogeneous in terms of their functions and phenotypes as a consequence of adaptation to different tissue environments. Local tissue-derived signals are thought to control functional polarization of resident macrophages; however, the identity of these signals remains largely unknown. It is also unknown whether functional heterogeneity is a result of irreversible lineage-specific differentiation or a consequence of continuous but reversible induction of diverse functional programs. Here, we identified retinoic acid as a signal that induces tissue-specific localization and functional polarization of peritoneal macrophages through the reversible induction of transcription factor GATA6. We further found that GATA6 in macrophages regulates gut IgA production through peritoneal B-1 cells. These results provide insight into the regulation of tissue-resident macrophage functional specialization by tissue-derived signals.

Subfields: Immunology, Molecular Biology, Representation & Self-Supervised Learning

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Citations in the corpus

Predicting multicellular function through multi-layer tissue networks (2017, background): “A unified view of human diseases and cellular functions across a broad range of human tissues is essential, not only for understanding basic biology but also for interpreting genetic variation and developing therapeutic strategies (Greene et al., 2015; GTEx et al., 2015; Okabe and Medzhitov, 2014; Y”
Progress in tumor-associated macrophage (TAM)-targeted therapeutics (2017, neutral): “2 Macrophage polarization Macrophages are a plastic cell type capable of reacting to microenvironmental cues [23].”
Macrophage Polarization: Different Gene Signatures in M1(LPS+) vs. Classically and M2(LPS–) vs. Alternatively Activated Macrophages (2019, background): “Since the discovery of tissue-specific gene signatures in peritoneal macrophages (6), many published transcriptomic data show that each tissue macrophage set has both tissue-specific and shared gene signatures, based on the tissue of origin (7).”
From Monocytes to M1/M2 Macrophages: Phenotypical vs. Functional Differentiation (2014, background): “Thus, as already mentioned above, it is logical to hypothesize that the subsets are varying mixtures of M1- and M2-type macrophages, as observed in the lung and in the peritoneal cavity, where tissue-specific variations in the balance of M1- and M2-type responses have been revealed (74, 186).”
The interaction of anticancer therapies with tumor-associated macrophages (2015, background): “The identification of genetic and epigenetic mechanisms (e.g., Ostuni et al., 2013; Okabe and Medzhitov, 2014; Rosas et al., 2014) underlying macrophage diversity in tissues and their different forms of activation is likely to pave the way to reeducation strategies.”
Tissue-Resident Macrophage Enhancer Landscapes Are Shaped by the Local Microenvironment (2014, background): “Therefore, Gata6 is a likely regulator of peritoneal-specific macrophage enhancers, as supported by recently published results (Gautier et al., 2014; Okabe and Medzhitov, 2014; Rosas et al., 2014).”
Macrophages: development and tissue specialization. (2015, background): “This suggests that a Gata-6-driven program can be initiated by both embryo-derived and adult BM-derived cells.”
An Apoptotic 'Eat Me' Signal: Phosphatidylserine Exposure. (2015, background): “However, macrophages in varying tissues have different gene expression profiles [45], supporting the idea that macrophages are heterogeneous [46].”
Macrophage heterogeneity in tissues: phenotypic diversity and functions (2014, background): “Okabe Y, Medzhitov R. Tissue-specific signals control reversible program of localization and functional polarization of macrophages.”