Figure 3.

Multiple effects of SAA may relate to its contribution in sarcoidosis pathogenesis. SAA levels are upregulated in response to (bacterial) antigens stimulating the innate immune system. SAA contributes in Th17-cell proliferation, Th17 cytokine production, and in M2 polarization of macrophages. Both Th17 cells as well as M2 macrophages are thought to be involved in sarcoidosis pathogenesis and granuloma formation. Accumulation of SAA might result in misfolding or aggregation of SAA and formation of complexes with other matrix proteins, leading to granuloma formation and entrapment of antigens. SAA serum levels and tissue expression may result in chronic inflammation and fibrosis. SAA levels may be further increase in response to fibrotic and hypoxic stimuli. Fibrosis is often accompanied by low-grade inflammation and tissue-barrier disruption, which may also lead to an upregulation of SAA levels since SAA contributes to (bacterial) antigen clearance. Created with BioRender.com (accessed on 3 March 2021).