Abstract
The etiology of sarcoidosis is unknown. In this study, Propionibacterium acnes (PA) was used to induce sarcoidosis-like granulomatous inflammation in a mouse model. Wild-Type (WT) C57BL/6 mice were divided into three groups: (1) WT-PA group; (2) WT-PA + Incomplete Freund's Adjuvant (IFA) group; and (3) WT-PBS group. Loose granuloma formation was observed in the lungs on day 56 in the WT-PA and WT-PA + IFA groups. The proportions of peripheral Th17 cells in the WT-PA (p = 0.0004) and WT-PA + IFA groups (p = 0.0005) were significantly higher than that in the WT-PBS group. The proportions of peripheral Treg cells in the WT-PA (p < 0.0001) and WT-PA + IFA groups (p < 0.0001) were lower than that in the WT-PBS group. Then, to explore the mechanism of IL-17, Wild-Type (WT) C57BL/6 mice were divided into three groups: (1) WT-PBS group (2) WT-PA group; (3) WT-PA + mouse IL-17A neutralizing antibody (IL-17Ab) group. IL-17A gene knockout mice (KO) were divided into two groups: (1) KO -PA group; (2) KO-PBS group. The KO-PA and WT-PA + IL-17Ab groups showed reduced inflammation and no loose granuloma formation on day 56. As compared to the WT-PA group, the ratio of peripheral Th17 in the KO-PA (p < 0.0001) and WT-PA + IL-17Ab groups (p < 0.0001) decreased, while the ratio of peripheral Treg in the KO-PA (p < 0.0001) and WT-PA + IL-17Ab (p = 0.0069) groups increased on day 56. Hence, PA can be used to establish a mouse model of sarcoidosis-like granuloma. IL-17A plays an important role in experimental sarcoidosis-like granuloma formation.
Highlights
Sarcoidosis, a systemic granulomatous disease of unknown etiology, is characterized by non-caseous necrotic granulomata [1]
Loose granulomatous tissue could be seen in the lung of mice from the WT-Propionibacterium acnes (PA) and WT-PA + Incomplete Freund’s Adjuvant (IFA) groups
Immunohistochemical, hexamine silver, and acid-fast staining of the lung tissue specimens on day 56 showed positive CD4 and CD68 but negative PAS, hexamine silver, and acid-fast (Figure 3A). These results indicated that the mouse model of PA-induced sarcoidosis-like granulomatosis has similar lung tissue characteristics as human granulomatosis, and fungal and tuberculosis bacterial infection can be excluded
Summary
Sarcoidosis, a systemic granulomatous disease of unknown etiology, is characterized by non-caseous necrotic granulomata [1]. The pathogenesis of sarcoidosis remains unclear, and may be associated with infection [2], genetics [3], immunity [4], and environmental exposure [5]. Previous studies have indicated that Propionibacterium acnes (PA) might be a causative pathogen for sarcoidosis [6,7,8]. Since the cause of sarcoidosis is unknown, a standardized animal model is lacking. Since 1998, PA has been used to successfully establish an animal model of liver granuloma [9]. Ichiyasu et al [10] used PA to induce sarcoidosis-like granulomatosis in rabbit lung.
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