CD 11b+Gr‐1 dim Tolerogenic Dendritic Cell–Like Cells Are Expanded in Interstitial Lung Disease in SKG Mice

Objective SKG mice develop interstitial lung disease ( ILD ) resembling rheumatoid arthritis–associated ILD in humans. The aim of this study was to clarify the mechanism underlying the lung pathology by analyzing lung‐infiltrating cells in SKG mice with ILD . Methods We assessed the severity of zymosan A (ZyA)–induced ILD in SKG mice histologically, and we examined lung‐infiltrating cells by flow cytometry. Total lung cells and isolated monocytic myeloid‐derived suppressor cells ( MDSC s) were cultured in vitro with granulocyte–macrophage colony‐stimulating factor ( GM ‐ CSF ) and interleukin‐4. The proliferation of 5,6‐carboxyfluorescein diacetate N ‐succinimidyl ester–labeled naive T cells cocultured with isolated CD 11b+Gr‐1 dim cells and MDSC s was evaluated by flow cytometry. CD 11b+Gr‐1 dim cells were adoptively transferred to ZyA‐treated SKG mice. Results MDSC s, Th17 cells, and group 1 and 3 innate lymphoid cells ( ILC 1s and ILC 3s) were increased in the lungs; the proportion of these cells varied with ILD severity. In this process, we found that a unique cell population, CD 11b+Gr‐1 dim cells, was expanded in the severely inflamed lungs. Approximately half of the CD 11b+Gr‐1 dim cells expressed CD 11c. CD 11b+Gr‐1 dim cells were induced from monocytic MDSC s with GM ‐ CSF in vitro and were considered tolerogenic because they suppressed T cell proliferation. These CD 11b+Gr‐1 dim cells have never been described previously, and we termed them CD 11b+Gr‐1 dim tolerogenic dendritic cell ( DC )–like cells. Th17 cells, ILC 1s, and ILC 3s in the inflamed lung produced GM ‐ CSF , which may have expanded CD 11b+Gr‐1 dim tolerogenic DC –like cells in vivo. Furthermore, adoptive transfer of CD 11b+Gr‐1 dim tolerogenic DC –like cells significantly suppressed progression of ILD in SKG mice. Conclusion We identified unique suppressive myeloid cells that were differentiated from monocytic MDSC s in SKG mice with ILD , and we termed them CD 11b+Gr‐1 dim tolerogenic DC –like cells.