Figure 1.

Schematic of the current state of the genetic, immunological, and environmental basis of sarcoidosis. Environmental triggers, mostly microbial in origin, interact with genetic, epigenetic, environmental, and immunologic host factors resulting in a hyperpolarized T-helper (Th)1 response to pathogenic tissue antigens and epithelioid granuloma formation. The local Th1 immune responses are associated with impaired regulatory T-cell function and innate immune stimulation (e.g., Toll-like receptor 2, serum amyloid A). The determinants of the different clinical phenotypes and outcomes remain uncertain. *There is a lack of consensus on whether inorganic agents can trigger multisystem sarcoidosis. MHC = major histocompatibility complex; TNF = tumor necrosis factor.