Transcriptional control of macrophage diversity and specialization

Abstract

The key driving force underlying cell identity is represented by the complex and dynamic interplay between cell‐intrinsic, lineage‐restricted developmental pathways on the one hand, and cell‐extrinsic, tissue‐specific microenvironmental signals on the other. In this context, macrophages are a paradigmatic cell population whose functional specialization in vivo reflects the impact of the local microenvironment on the intrinsic differentiation program, leading to a variety of specialized macrophage types in different tissues and conditions; however, how this is translated into a biological outcome is not appreciably understood. The kind of investigations described in this Viewpoint aim to explore the inner determinants of cell identity and functional diversification at a genomic level; mechanisms that permit plastic cell types, like macrophages, to adapt to different environments.

Intestinal macrophages – specialised adaptation to a unique environment

“…Thus resident intestinal Mjs seem to be in a state of partial activation, contributing to intestinal homeostasis through the production of immunoregulatory cytokines and by the clearance of commensal bacteria that breach the epithelial barrier without provoking an inflammatory response. As others will discuss in this Viewpoint series [26][27][28][29], several activation states have now been described for Mjs in other tissues, including classically (M1) and alternatively (M2) activated Mjs [30] (Table 1). Resident intestinal Mjs are clearly not similar to the pro-inflammatory population of M1 Mjs; they also do not fit precisely with the M2 subset of Mjs associated with wound healing and tissue repair.…”

Diversity and plasticity of mononuclear phagocytes

“…The study of the regulation of gene expression by transcription control [9] and of epigenetic control of macrophage polarisation [10] is in its infancy but promises to provide important insights into macrophage differentiation and activation. Chromatin statusmediated regulation of promoter activity and enhancers, together with repressors, controls basal and inducible gene expression in macrophages, which provides an excellent model for further research.…”

“…F4/80 À precursors able to give rise to F4/80 1 Mfs in culture can be isolated from embryos at d4. F4/80 1 cells appear widely in non-haemopoietic tissues from d9, and are phagocytic for apoptotic cells, for example in the nervous system and during tissue remodelling in the interdigital web of limb buds [9].…”

Contribution of myeloid cell subsets to liver fibrosis in parasite infection

“…The differentiation and polarization of myeloid cells can be regulated by dynamic changes in transcription factors and miRNA expression and by epigenetic regulation, including DNA methylation and histone modifications by methyltransferases, demethylases, acetyltransferases and deacetylases [107,[168][169][170][171][172][173][174]. Thus, it will be important to investigate whether Th2 priming by DCs and M2 subsets development are dependent on these processes and which genes are targeted, with the aim of identifying specific mechanisms promoting the development of fibrosis in parasite infection.…”