Functional Role Of Fc Gamma Riib In The Regulation Of Mesenchymal Stem Cell Function

Mesenchymal stem cells (MSCs) derived from bone marrow are plural-potent stem cells with immune regulatory functions. We aimed to evaluate role of Fc gamma RIIB in the regulation of bone marrow-derived MSC function. MSCs were prepared from mouse bone marrow derived from wild-type (WT) or Fc gamma RIIB-deficient (Fc gamma RIIB-/-) 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 Fc gamma RIIB-/- 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 Fc gamma RIIB expression. Fc gamma RIIB deficiency impaired the suppressive function of MSCs, as Fc gamma RIIB deficiency efficiently reversed the inhibitory effect of MSCs on BMDC maturation and function. Additionally, Fc gamma RIIB-/-MSCs were less potent at suppressing asthma in model mice, possibly through reduced expression of Smad2, Smad3, Cox-2, and prostaglandin E2 in Fc gamma RIIB-/-MSCs. Fc gamma RIIB might play an essential role in regulating the inhibitory effects of MSCs derived from bone marrow.