Sarcoidosis is a severe inflammatory disorder that can involve multiple organs, particularly the lungs and lymph nodes. Bone marrow-derived mesenchymal stromal cells (MSCs) have the ability to “reprogram” various macrophage populations toward an anti-inflammatory phenotype. This study investigated whether alveolar macrophages from sarcoidosis patients exhibit a similar anti-inflammatory response when co-cultured with MSCs. Bronchoscopy and bronchoalveolar lavage (BAL) were performed on fifteen sarcoidosis patients and eight healthy controls. Unselected BAL cells, comprising 70–94% macrophages, were isolated and cultured with or without MSCs derived from healthy donors. After stimulating the cultures with lipopolysaccharide, supernatants were collected to measure levels of interleukin-10 (IL-10) and tumor necrosis factor-alpha (TNF-α). In two additional sarcoidosis patients, flow cytometry was used to evaluate intracellular cytokines and surface markers to validate the findings. In nine out of eleven sarcoidosis samples, co-culture with MSCs resulted in decreased TNF-α (indicative of pro-inflammatory M1 activity) and increased IL-10 (indicative of anti-inflammatory M2 activity). BAL cells from control subjects displayed minimal changes in cytokine production. Flow cytometric analysis in the additional patients confirmed a shift of alveolar macrophages from a pro-inflammatory (M1) to an anti-inflammatory (M2) state following MSC co-culture. These findings indicate that alveolar macrophages, like other macrophage populations, can adopt an anti-inflammatory phenotype in response to MSC interaction. We propose that administering MSCs to the airways could potentially reduce lung inflammation and lower the need for corticosteroids in patients with sarcoidosis.
