| First Author | Minasyan M | Year | 2021 |
| Journal | Am J Physiol Lung Cell Mol Physiol | PubMed ID | 33851886 |
| Mgi Jnum | J:304726 | Mgi Id | MGI:6695013 |
| Doi | 10.1152/ajplung.00575.2020 | Citation | Minasyan M, et al. (2021) Elevated IL-15 concentrations in the sarcoidosis lung is independent of granuloma burden and disease phenotypes. Am J Physiol Lung Cell Mol Physiol |
| abstractText | Sarcoidosis is a systemic granulomatous disease predominantly affecting the lungs. The mechanisms promoting disease pathogenesis and progression are unknown, although interleukin-15 (IL-15) has been associated with the immune-mediated inflammation of sarcoidosis. Because the identification of a mechanistically-based, clinically-relevant biomarker for sarcoidosis remains elusive, we hypothesized this role for IL-15. Pulmonary sarcoidosis granuloma formation was modeled using trehalose 6,6'-dimicolate (TDM), which was administered into wild-type and three lineages of mice: those over-expressing IL-15, deficient in IL-15, and deficient in IL-15 receptor alpha. The number of granulomas per lung was counted and normalized to the wild-type. IL-15 concentrations were measured in the bronchoalveolar lavage (BAL) from healthy controls and sarcoidosis subjects in our cohort, where associations between IL-15 levels and clinical manifestations were sought. Findings were validated in another independent sarcoidosis cohort. TDM administration resulted in similar granuloma numbers across all lineages of mice. IL-15 concentrations were elevated in the BAL of both human cohorts, irrespective of disease phenotypes. In exploratory analysis, an association with obesity was observed, and various other soluble mediators were identified in the BAL of both cohorts. Although IL-15 is enriched in the sarcoidosis lung, it was independent of disease pathogenesis or clinical manifestations in our mouse model and human cohorts of sarcoidosis. An association with obesity perhaps reflects the ongoing inflammatory processes of these co-morbid conditions. Our findings showed that IL-15 is redundant for disease pathogenesis and clinical progression of sarcoidosis. |
