Macrophage Polarization in Sarcoidosis: An Unexpected Accomplice?

Sarcoidosis is a complex immune disease characterized by accumulation of antigen-activated CD4 T cells and macrophages, progressing to granuloma formation. Granulomas result from a dynamic interplay between macrophages and T lymphocytes. Granulomatous inflammation in pulmonary sarcoidosis has historically been linked to compartmentalized elevation of T-helper cell type 1 (Th1) cytokines, including but not limited to IL-2, IFN-γ, and TNF-α. This cytokine milieu is believed to drive classical (M1) macrophage activation. Emerging data, including the findings of Locke and colleagues presented in this issue of the Journal, challenge the paradigm that granulomatous inflammation in sarcoidosis is simply a Th1-mediated process, and suggest that this tissue response is much more contextual and nuanced. Finally, the durability and reversibility of macrophage skewing is unknown and requires further investigation. Regardless, this timely study sheds fresh new light on pathogenic mechanisms in sarcoidosis and identifies additional potential accomplices involved in this disease.