Tissue-Specific Signals Control Reversible Program of Localization and Functional Polarization of Macrophages

Abstract

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.

NADPH oxidase controls neutrophilic response to sterile inflammation in mice by regulating the IL-1α/G-CSF axis

“…27,35,36 Peritoneal IL-1a levels at 4 hours following periodate injury were similarly reduced in GATA6 Dmac mice compared with GATA6 flox/flox (supplemental Figure 8). However, the IL-1b responses were unaffected, suggesting that this isoform is derived from recruited exudate leukocytes.…”

Neutrophil derived CSF1 induces macrophage polarization and promotes transplantation tolerance

“…Monocytes differentiate into classically (Ly6C hi /M1) or alternatively (Ly6C lo /M2) activated macrophages according to the local environment (7, 8). Inflammatory Ly6C hi monocytes are rapidly recruited to inflamed tissues and become alternatively activated Ly6C lo macrophages once the inciting inflammatory stimulus has been resolved (9).…”

The origin and function of tumor-associated macrophages

“…10 Furthermore, the localization of tissue-specific macrophages and the polarization of macrophage function can be determined, at least partially, by this pathway. 11 Several cytokines, such as IL-6, have been found to be important in the development and maintenance of the macrophage subsets and their functions in inflammation and tissue homeostasis. 12 Much work has been performed to identify the soluble factors, such as chemokines and growth factors, in polarizing macrophage function in tumor progression.…”