Culture medium from TNF-α-stimulated mesenchymal stem cells attenuates allergic conjunctivitis through multiple antiallergic mechanisms

JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY

卷:136

Article

Su, Wenru^1,2  Wan, Qian¹  Huang, Jingwen¹  Han, Longhui¹  Chen, Xiaoqing^1,3  Chen, Guihua²  Olsen, Nancy³  Zheng, Song Guo^2,3  Liang, Dan¹ 

[1] Sun Yat Sen Univ, Zhongshan Ophthalm Ctr, State Key Lab Ophthalmol, Guangzhou 510275, Guangdong, Peoples R China

[2] Sun Yat Sen Univ, Affiliated Hosp 1, Ctr Clin Immunol, Guangzhou 510275, Guangdong, Peoples R China

[3] Penn State Univ, Hershey Coll Med, Dept Med, Div Rheumatol, Hershey, PA USA

关键词: Allergy;    mesenchymal stem cells;    stems cells;    B cells;    mast cells;    histamine;    allergic conjunctivitis;   

DOI  :  10.1016/j.jaci.2014.12.1926

来源: Elsevier

【 摘 要 】

Background: The immunomodulatory and anti-inflammatory functions of mesenchymal stem cells (MSCs) have been demonstrated in several autoimmune/inflammatory diseases, but their contribution to allergic conjunctivitis and underlying antiallergic mechanisms remain elusive. Objective: We sought to explore the clinical application of MSCs to experimental allergic conjunctivitis (EAC) and its underlying antiallergic mechanisms. Methods: Culture medium from TNF-alpha-stimulated, bone marrow-derived MSCs (MSC-CMT) was administered topically to mice with EAC, and the related allergic symptoms and biological changes were evaluated. Murine spleen-derived B cells, bone marrow-derived mast cells (MCs), and lung vascular endothelial cells were cultured in vitro to investigate the antiallergic MSC-CMT mechanisms. Results: Topical instillation of MSC-CMT significantly attenuated the clinical symptoms of short ragweed pollen-induced EAC, with a significant decrease in inflammatory cell frequency, nuclear factor kB p65 expression, and TNF-alpha and IL-4 production. In vitro MSC-CMT significantly inhibited the activation of MCs and B-cell IgE release and reduced histamine-induced vascular hyperpermeability. During EAC, MSC-CMT treatment also decreased IgE production, histamine release, enrichment and activation of MCs, and conjunctival vascular hyperpermeability. The MSC-CMT-mediated inhibition of B cells, MCs, and histamine and its antiallergic effects during EAC were abrogated when MSCs were pretreated with COX2 small interfering RNA. Conclusions: Our findings provide compelling evidence that MSC-CMT inhibits EAC through COX2-dependent multiple antiallergic mechanisms and support the use of MSC-CMT as a novel strategy for treating allergic conjunctivitis.

【 授权许可】

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