SOCS Proteins in Macrophage Polarization and Function.

Heather M Wilson

doi:10.3389/fimmu.2014.00357

Abstract

Macrophages were initially described as “big eaters” due to their phagocytic nature. It is now clear that macrophages have many diverse functions not only in innate immunity and tissue homeostasis but also in metabolism, development, and regeneration. Macrophage functions are driven largely by tissue-derived and pathogenic microenvironmental stimuli that help them adapt to changing conditions within tissues and tailor an appropriate response. The heterogeneity of macrophages has resulted in their classification into subtypes based on their phenotype and function (1). One major classification, based on function, is M1 and M2 macrophages, with destructive and healing properties, respectively (2, 3). As imbalances between M1 and M2 states have been observed in a number of diseases, an understanding of the molecular mechanisms, signaling pathways, and transcription factors controlling their polarization has obvious therapeutic implications. Recent studies have established strong potential for suppressor of cytokine signaling (SOCS) proteins to regulate M1 and M2 macrophage polarization (4–7). Here, the focus will be on the evidence for this, and the consequences of altered SOCS expressions on macrophage function in health and disease. Overall it is proposed that a high SOCS1 to SOCS3 ratio could be a potential marker for M2 macrophages while high SOCS3 expression is associated with M1 cells.

Highlights

Macrophages were initially described as “big eaters” due to their phagocytic nature
Overall it is proposed that a high SOCS1 to SOCS3 ratio could be a potential marker for M2 macrophages while high SOCS3 expression is associated with M1 cells
Expression of macrophage SOCS1, but not SOCS3, is strongly upregulated in an M2 polarizing environment in vitro and in vivo, where it has an important role in acquisition of M2 functional characteristics, such as a high arginase I/low inducible nitric oxide synthase expression ratio [4]

Summary

INTRODUCTION

Macrophages were initially described as “big eaters” due to their phagocytic nature. It is clear that macrophages have many diverse functions in innate immunity and tissue homeostasis and in metabolism, development, and regeneration. SOCS1 SOCS1 regulates M1-macrophage activation by inhibiting the interferon gamma-induced JAK2/STAT1 pathway and TLR/NF-κB signaling [9, 15] (Figure 1). Expression of macrophage SOCS1, but not SOCS3, is strongly upregulated in an M2 polarizing environment in vitro and in vivo, where it has an important role in acquisition of M2 functional characteristics, such as a high arginase I/low inducible nitric oxide synthase (iNOS) expression ratio [4]. This contrasts with macrophages infiltrating an in vivo inflamed M1-activating environment, where macrophages with www.frontiersin.org

SOCS proteins and macrophage polarization

Findings

CONCLUSION AND PERSPECTIVES