IL-17A Can Promote Propionibacterium acnes-Induced Sarcoidosis-Like Granulomatosis in Mice

Song, Jukun; Zhao, Mengmeng; Li, Qiuhong; Lu, Liqin; Zhou, Ying; Zhang, Yuan; Chen, Tao; Tang, Dan-Li; Zhou, Nian-Yu; Yin, Chengsheng; Wu, Dong; Li, Huiping

doi:10.3389/fimmu.2019.01923

Cited by 13 publications

(7 citation statements)

References 38 publications

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“…So far, no specific C. acnes phylotype has been associated with sarcoidosis. The involvement of C. acnes in sarcoidosis is also supported by experiments in mice (Werner et al, 2017;Song et al, 2019). As a possible disease scenario, invasive C. acnes, possibly derived from the skin, could result in a latent, intracellular state, for example in macrophages.…”

Section: Sarcoidosismentioning

confidence: 80%

A Janus-Faced Bacterium: Host-Beneficial and -Detrimental Roles of Cutibacterium acnes

et al. 2021

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The bacterial species Cutibacterium acnes (formerly known as Propionibacterium acnes) is tightly associated with humans. It is the dominant bacterium in sebaceous regions of the human skin, where it preferentially colonizes the pilosebaceous unit. Multiple strains of C. acnes that belong to phylogenetically distinct types can co-exist. In this review we summarize and discuss the current knowledge of C. acnes regarding bacterial properties and traits that allow host colonization and play major roles in host-bacterium interactions and also regarding the host responses that C. acnes can trigger. These responses can have beneficial or detrimental consequences for the host. In the first part of the review, we highlight and critically review disease associations of C. acnes, in particular acne vulgaris, implant-associated infections and native infections. Here, we also analyse the current evidence for a direct or indirect role of a C. acnes-related dysbiosis in disease development or progression, i.e., reduced C. acnes strain diversity and/or the predominance of a certain phylotype. In the second part of the review, we highlight historical and recent findings demonstrating beneficial aspects of colonization by C. acnes such as colonization resistance, immune system interactions, and oxidant protection, and discuss the molecular mechanisms behind these effects. This new insight led to efforts in skin microbiota manipulation, such as the use of C. acnes strains as probiotic options to treat skin disorders.

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Section: Sarcoidosismentioning

confidence: 80%

A Janus-Faced Bacterium: Host-Beneficial and -Detrimental Roles of Cutibacterium acnes

et al. 2021

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“…First, SAA was found to contribute to Th17-cell proliferation and Th17 cytokine production [ 8 ]. Th17-cells have been found to contribute in sarcoidosis pathogenesis [ 9 , 10 ] and in granuloma formation [ 11 , 12 ]. Second, Chen et al [ 13 ] studied the role of SAA in the regulation of granulomatous inflammation in sarcoidosis and found significant presence of SAA in granulomas of sarcoidosis patients which exceeded the intensity of SAA staining found in tissue from patients with tuberculosis, granulomatous polyangiitis, or hypersensitivity pneumonitis [ 13 ].…”

Section: Introductionmentioning

confidence: 99%

Elevated Serum Amyloid a Levels Are not Specific for Sarcoidosis but Associate with a Fibrotic Pulmonary Phenotype

Beijer

Roodenburg-Benschop

Schimmelpennink

et al. 2021

Cells

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Elevated Serum Amyloid A (SAA) levels have been found in several inflammatory diseases, including sarcoidosis. SAA is suggested to be involved in sarcoidosis pathogenesis by involvement in granuloma formation and maintenance. We hypothesized that SAA serum levels would be higher in sarcoidosis compared to other non-infectious granulomatous and non-granulomatous diseases. SAA levels were measured in serum from sarcoidosis, Hypersensitivity pneumonitis (HP), and (eosinophilic) granulomatosis with polyangiitis ((E)GPA) patients. Idiopathic pulmonary fibrosis (IPF) patients were included as non-granulomatous disease group. SAA levels of patients with sarcoidosis (31.0 µg/mL), HP (23.4 µg/mL), (E)GPA (36.9 µg/mL), and IPF (22.1 µg/mL) were all higher than SAA levels of healthy controls (10.1 µg/mL). SAA levels did not differ between the diagnostic groups. When SAA serum levels were analyzed in sarcoidosis subgroups, fibrotic sarcoidosis patients showed higher SAA levels than sarcoidosis patients without fibrosis (47.8 µg/mL vs. 29.4 µg/mL, p = 0.005). To conclude, the observation that fibrotic sarcoidosis patients have higher SAA levels, together with our finding that SAA levels were also increased in IPF patients, suggests that SAA may next to granulomatous processes also reflect the process of fibrogenesis. Further studies should clarify the exact role of SAA in fibrosis and the underlying mechanisms involved.

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“…The mechanism of IL-35 in granulomatous inflammation was further analyzed using a mouse model of sarcoidosis granuloma which was previously established by our study group (20). The findings suggested that IL-35 and IL-21 levels in the BALF of mouse models of sarcoidosis granuloma were elevated, and the proportions of Bregs and Tfh cells in the peripheral blood and BALF also increased, however the proportion of Tregs decreased.…”

Section: Discussionmentioning

confidence: 70%

Serum IL-35 Levels Are Associated With Activity and Progression of Sarcoidosis

Zhao

Song

et al. 2020

Front. Immunol.

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Objective: To investigate the relationship of interleukin (IL)-35 with sarcoidosis.Methods: We enrolled 114 inpatients and outpatients with sarcoidosis at the Shanghai Pulmonary Hospital, and 24 healthy controls between March 2015 and December 2017. Serum and whole blood were collected during the follow-up period. Serum IL-35 levels were detected by ELISA. Proportions of Breg, Tfh, and Treg cells in the peripheral blood were detected using flow cytometry (FCM). The mRNA levels of p35, EBI3, and GAPDH in CD19 + cells and CD4 + cells were detected by real-time PCR. Sarcoidosis granuloma mice models were established with Propionibacterium acnes (PA) and one group was treated with IL-35 antibodies. Proportions of Breg, Tfh, and Treg cells in the peripheral blood and bronchoalveolar lavage fluid (BALF) were detected by FCM. Results:The IL-35 levels and the proportions of Breg and Tfh cells in the peripheral blood of patients with active sarcoidosis were significantly higher compared to patients with stable sarcoidosis and healthy controls. Moreover, the IL-35 level in patients with progressive disease was lower than that found at the initial visit. EBI3 and p35 mRNA levels in CD19 + cells for patients with active sarcoidosis were significantly higher as compared to patients with stable sarcoidosis and healthy controls, while there were no significant differences in p35 and EBI3 mRNA levels in CD4 + cells between the three groups. In the mouse model of sarcoidosis, there were loose granulomata (macrophage accumulation in the bronchial areas and immature granuloma) after intervention with IL-35 antibodies. Meanwhile, the proportions of Breg cells in the peripheral blood and BALF of the model were significantly increased, while the proportion of Treg cells declined significantly. After intervention with IL-35 antibodies, the proportion of Breg cells in the peripheral blood of mice decreased significantly as compared to the mice not exposed to anti-IL-35 antibodies.Conclusion: IL-35 levels increased significantly in the serum of patients with active sarcoidosis, and lower IL-35 levels were correlated with persistent disease. Serum IL-35 levels might be better correlated with Breg cell functions.

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IL-17A Can Promote Propionibacterium acnes-Induced Sarcoidosis-Like Granulomatosis in Mice

Cited by 13 publications

References 38 publications

A Janus-Faced Bacterium: Host-Beneficial and -Detrimental Roles of Cutibacterium acnes

A Janus-Faced Bacterium: Host-Beneficial and -Detrimental Roles of Cutibacterium acnes

Elevated Serum Amyloid a Levels Are not Specific for Sarcoidosis but Associate with a Fibrotic Pulmonary Phenotype

Serum IL-35 Levels Are Associated With Activity and Progression of Sarcoidosis

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