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CD11b+Gr-1 dim Tolerogenic Dendritic Cell-Like Cells Are Expanded in Interstitial Lung Disease in SKG Mice

CD11b+Gr-1 dim Tolerogenic Dendritic Cell-Like Cells Are Expanded in Interstitial Lung Disease in SKG Mice

Sho Sendo, Jun Saegusa, Takaichi Okano, Soshi Takahashi, Kengo Akashi, Akio Morinobu

Arthritis Rheumatol. 2017 Dec;69(12):2314-2327.

PMID: 28805019

Abstract:

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 (MDSCs) 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 CD11b+Gr-1dim cells and MDSCs was evaluated by flow cytometry. CD11b+Gr-1dim cells were adoptively 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+Gr-1dim cells, was expanded in the severely inflamed lungs. Approximately half of the CD11b+Gr-1dim cells expressed CD11c. CD11b+Gr-1dim cells were induced from monocytic MDSCs with GM-CSF in vitro and were considered tolerogenic because they suppressed T cell proliferation. These CD11b+Gr-1dim cells have never been described previously, and we termed them CD11b+Gr-1dim tolerogenic dendritic cell (DC)-like cells. Th17 cells, ILC1s, and ILC3s in the inflamed lung produced GM-CSF, which may have expanded CD11b+Gr-1dim tolerogenic DC-like cells in vivo. Furthermore, adoptive transfer of CD11b+Gr-1dim tolerogenic DC-like cells significantly suppressed progression of ILD in SKG mice.
Conclusion:
We identified unique suppressive myeloid cells that were differentiated from monocytic MDSCs in SKG mice with ILD, and we termed them CD11b+Gr-1dim tolerogenic DC-like cells.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
AP150347594	5(6)-Carboxyfluorescein diacetate N-succinimidyl ester		150347-59-4	Price

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