Sarcoidosis is a devastating inflammatory disease affecting many organs, especially
the lungs and lymph nodes. Bone marrow-derived mesenchymal stromal cells (MSCs) can
"reprogram" various types of macrophages towards an anti-inflammatory phenotype. We
wanted to determine whether alveolar macrophages from sarcoidosis subjects behave
similarly by mounting an anti-inflammatory response when co-cultured with MSCs. Fifteen
sarcoidosis and eight control subjects underwent bronchoscopy and bronchoalveolar
lavage (BAL). Unselected BAL cells (70-94% macrophages) were isolated and cultured
with and without MSCs from healthy adults. Following stimulation of the cultured cells
with lipopolysaccharide, the medium was removed to measure interleukin 10 and tumor
necrosis factor alpha (IL-10 and TNF-alpha). In two additional sarcoidosis subjects,
flow cytometry was used to study intracellular cytokines and surface markers associated
with alveolar macrophages to confirm the results. Unselected BAL cells from sarcoidosis
subjects co-cultured with MSCs showed a reduction in TNF-alpha (pro-inflammatory M1)
and an increase in IL-10 (anti-inflammatory M2) in 9 of 11 samples studied. Control
subject samples showed few, if any, differences in cytokine production. Unselected
BAL cells from two additional patients analyzed by flow cytometry confirmed a switch
towards an anti-inflammatory state (i.e., M1 to M2) after co-culture with MSCs. These
results suggest that, similarly to other macrophages, alveolar macrophages also respond
to MSC contacts by changing towards an anti-inflammatory phenotype. Based on our results,
we hypothesize that mesenchymal stromal cells applied to the airways might alleviate
lung inflammation and decrease steroid need in patients with sarcoidosis.
