Cytokines 2017

Objective. SKG mice develop interstitial lung disease (ILD) resembling rheumatoid arthritis-associated ILD (RA-ILD) in human. We identified a new cell population, CD11b⁺Gr1^dim cells, in the lung of ILD-induced SKG mice. The aims of this study are to elucidate the roles of lung-infiltrating cells, especially CD11b⁺Gr1^dim cells, in the pathogenesis of ILD in SKG mice.

Methods. We assessed the severity of zymosan A (ZyA)-induced ILD in SKG mice histologically, and examined lung-infiltrating cells by flow cytometry. Total lung cells and isolated monocytic myeloid-derived suppressor cells (M-MDSCs) were cultured in vitro with GM-CSF (and IL-4). The proliferation of CSFE-labeled naïve T cells co-cultured with isolated CD11b⁺Gr1^dim cells and MDSCs was evaluated by flow cytometry. CD11b⁺Gr1^dim cells were transferred to ZyA-treated SKG mice.

Results. MDSCs, Th17 cells, and group 1 and 3 innate lymphoid cells (ILC1s and ILC3s) were increased in the lungs; the proportion of these cells varied with ILD severity. In this process, we found that a unique cell population, CD11b⁺Gr1^dim cells, were expanded in the severely inflamed lungs. About half of the CD11b⁺Gr1^dim cells expressed CD11c. The CD11b⁺Gr1^dim cells were induced from M -MDSCs with GM-CSF in vitro and were considered tolerogenic because they suppressed T-cell proliferation. The CD11b⁺Gr1^dim cells have never described previously and termed CD11b⁺Gr1^dim tolerogenic dendritic cell-like cells (CD11b⁺Gr1^dim tolDC-LCs). Th17 cells, ILC1s and ILC3s in the inflamed lung produced GM-CSF, which may expand CD11b⁺Gr1^dim tolDC-LCs in vivo. Furthermore, adoptive transfer of CD11b⁺Gr1^dim tolDC-LCs significantly suppressed the progression of ILD in SKG mice.

Conclusion. We identified a unique cell population, termed CD11b⁺Gr1^dim tolDC-LCs, in ILD of SKG mice, and the cells could be a potential target for the treatment of RA-ILD.