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Sarcoidosis is a granulomatous disease of unknown etiology, with limited therapeutic options. Chronic sarcoidosis can result in pulmonary fibrosis and can be lethal. Enhanced expression of pro-inflammatory cytokines, such as interleukin-17A (IL-17A), has been observed in sarcoid granulomas in humans. However, the role of IL-17A in the pathogenesis of chronic sarcoidosis or sarcoidosis-related pulmonary fibrosis and its potential therapeutic effects remain unclear. This study investigated whether IL-17A is critical in granulomatosis and its role in chronic inflammation in a profibrotic manner. Wild-type and IL-17A-knockout C57BL/6 mice were repeatedly challenged with heat-killed Propionibacterium acnes (PA) to induce sarcoidosis-like granulomata and sarcoidosis-related pulmonary fibrosis. Wild-type mice with granulomatosis were treated with anti-IL-17A antibody. Administration of PA enhanced the expression of IL-17A, granulomatosis, and fibrosis in mouse lungs after boost stimulation. Neither granulomata nor fibrosis were observed in IL-17A-knockout mice, even in the presence of interferon-γ enhancement. Neutralizing IL-17A antibody reduced inflammatory cells in bronchoalveolar lavage fluid and ameliorated both granulomatosis and fibrosis in sarcoidosis mice. In conclusion, our data demonstrate that IL-17A plays a critical role in PA-induced sarcoidosis-like inflammation in both granulomatosis inflammation and disease progression to pulmonary fibrosis, thus providing novel insights into the treatment of chronic sarcoidosis or sarcoidosis-related pulmonary fibrosis., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Objectives: We sought to evaluate the prognostic value of blood routine parameters and biochemical parameters, especially inflammation-related biomarkers, and establish an inflammation-related prognostic model in Chinese patients with idiopathic pulmonary fibrosis (IPF)., Material/methods: Patients diagnosed as IPF at Beijing Chaoyang Hospital and aged 40 years and older were consecutively enrolled from June 2000 to March 2015, and finally, a total of 377 patients were enrolled in the derivation cohort. The follow-up ended in December 2016. We used Cox proportional hazard model to calculate the hazard ratio (HR) and establish the prognostic model. The discrimination and calibration of the prognostic model were evaluated in an independent validation cohort enrolled from China-Japan Friendship Hospital between January 2015 and December 2019., Results: Multivariate analysis revealed that patients with elevated monocyte-to-red blood cell count ratio (MRR) and monocyte counts showed increased risk of mortality. The clinical-physiological-biomarker (CPB) index and CPB stage we established in this study were a significant predictor, and the C-index for CPB index and CPB stage in the validation cohort was 0.635 (95% CI: 0.558-0.712) and 0.619 (95% CI: 0.544-0.694), respectively. Patients in CPB stage III had the poorest survival., Conclusion: We developed and validated a new inflammation-related prognostic model (CPB index and CPB stage) which was integration of age, gender, FVC (%, predicted), DLCO (%, predicted), Charlson Comorbidity Index, and blood monocyte counts. This prediction model exhibited strong ability in predicting mortality in Chinese patients with IPF., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Zhang, Ren, Xie, Ye, Ban, Zhang, Zhu, Liu, Wang, Geng, He, Jiang, He, Shu, Luo, Wang, Song, Fan, Sun and Dai.)

Sarcoidosis is a granulomatous disease of unknown etiology, immunologically characterized by a Th1 immune response. Transcriptome-wide expression studies in various types of sarcoid tissues contributed to better understanding of disease mechanisms. We performed a systematic database search on Gene Expression Omnibus (GEO) and utilized transcriptomic data from blood and sarcoidosis-affected tissues in a meta-analysis to identify a cross-tissue, cross-platform signature. Datasets were further separated into training and testing sets for development of a diagnostic classifier for sarcoidosis. A total of 690 differentially expressed genes were identified in the analysis among various tissues. 29 of the genes were robustly associated with sarcoidosis in the meta-analysis both in blood and in lung-associated tissues. Top genes included LINC01278 ( P = 3.11 × 10 -13 ), GBP5 ( P = 5.56 × 10 -07 ), and PSMB9 ( P = 1.11 × 10 -06 ). Pathway enrichment analysis revealed activated IFN-γ, IL-1, and IL-18, autophagy, and viral infection response. IL-17 was observed to be enriched in peripheral blood specific signature genes. A 16-gene classifier achieved excellent performance in the independent validation data (AUC 0.711-0.964). This study provides a cross-tissue meta-analysis for expression profiles of sarcoidosis and identifies a diagnostic classifier that potentially can complement more invasive procedures., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Jiang, Jiang, Costabel, Dai and Wang.)

Idiopathic pulmonary fibrosis (IPF) is a progressive and fatal disease and considered as a cancer-like disease. The phosphatase and tensin homologue deleted on chromosome 10 (PTEN) tumor suppressor has drawn attention in the pathogenesis of IPF. However, the role of PTEN in phenotypic transformation of lung fibroblasts, particularly in the migratory and invasive phenotype, is still elusive. Our data showed that PTEN expression was markedly reduced in both fibroblasts and myofibroblasts from IPF patients. Furthermore, loss of PTEN led to the transformation of normal fibroblasts to myofibroblasts and increased proliferation, apoptosis resistance, and migration/invasion activities. PTEN deficiency upregulated hyaluronan synthase 2 expression and thereby enhanced the invasion ability of fibroblasts. Cross-talk between PTEN and the transforming growth factor β1 (TGF-β1) pathway and PTEN reduction by hypoxia were observed. These findings suggest that PTEN is implicated in multiple pathways and plays a crucial role in the pathogenesis of IPF., (© 2015 by the Society for Experimental Biology and Medicine.)