1. Department of Respiratory, Changhai Hospital, Second Military Medical University, Shanghai 200433, China;
2. Department of Respiratory, The General Hospital of Shenyang Military, Shenyang, Liaoning, 110015, China;
3. Department of VIP Treatment, Changhai Hospital, Second Military Medical University, Shanghai 200433, China;
4. Department of Orthopedics, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, 210000, China;
5. Department of Immunology, Zhejiang University, Hangzhou, Zhejiang310000, China;
6. Department of Respiratory, No. 1 People's Hospital of Yancheng, Yancheng, Jiangsu, 224000, China;
7. Department of Respiratory, The 174 Hospital, Xiamen, Fujian, 361000, China
8. Institute of Immunology, The Second Military Medical University, Shanghai, 200433, China
* These authors contributed equally to this study.
Mesenchymal stem cells (MSCs) derived from bone marrow are plural-potent stem cells with immune regulatory functions. We aimed to evaluate role of FcγRIIB in the regulation of bone marrow-derived MSC function. MSCs were prepared from mouse bone marrow derived from wild-type (WT) or FcγRIIB-deficient (FcγRIIB-/-) mice. MSCs were co-cultured with bone marrow-derived dendritic cells (BMDCs), and BMDC maturation and function were evaluated by flow cytometric analysis and carboxyfluorescein succinimidyl ester-labeled OT-II T-cell addition. An acute asthma model was established by aeresol ovalbumin challenge in mice. Mice received WT or FcγRIIB-/- MSC therapy. Lung function was evaluated by histological examination and cytokine production measurement. mRNA and protein expression levels of target genes were examined by real-time quantitative polymerase chain reactionor western blotting. We found that MSCs derived from bone marrow exhibit a high level of FcγRIIB expression. FcγRIIB deficiency impaired the suppressive function of MSCs, as FcγRIIB deficiency efficiently reversed the inhibitory effect of MSCs on BMDC maturation and function. Additionally, FcγRIIB-/-MSCs were less potent at suppressing asthma in model mice, possibly through reduced expression of Smad2, Smad3, Cox-2, and prostaglandin E2 in FcγRIIB-/-MSCs. FcγRIIB might play an essential role in regulating the inhibitory effects of MSCs derived from bone marrow.
Keywords: mesenchymal stem cells, FcγRIIB, dendritic cell maturation, asthma.