SOCS Proteins in Macrophage Polarization and Function

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.