期刊
STEM CELLS
卷 33, 期 4, 页码 1254-1266出版社
WILEY
DOI: 10.1002/stem.1913
关键词
Mesenchymal stem cells; Atopic dermatitis; Mast cell degranulation; Immunomodulation; NOD2
资金
- Bio & Medical Technology Development Program of the National Research Foundation (NRF) - Ministry of Science, ICT, & Future Planning [2012M3A9C6049716]
- Korean Health Technology R&D Project, Ministry of Health & Welfare, Republic of Korea [A120176]
- National Research Foundation of Korea [2012M3A9C6049716] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)
Mesenchymal stem cell (MSC) is a promising tool for the therapy of immune disorders. However, their efficacy and mechanisms in treating allergic skin disorders are less verified. We sought to investigate the therapeutic efficacy of human umbilical cord blood-derived MSCs (hUCB-MSCs) against murine atopic dermatitis (AD) and to explore distinct mechanisms that regulate their efficacy. AD was induced in mice by the topical application of Dermatophagoides farinae. Naive or activated-hUCB-MSCs were administered to mice, and clinical severity was determined. The subcutaneous administration of nucleotide-binding oligomerization domain 2 (NOD2)-activated hUCB-MSCs exhibited prominent protective effects against AD, and suppressed the infiltration and degranulation of mast cells (MCs). A -hexosaminidase assay was performed to evaluate the effect of hUCB-MSCs on MC degranulation. NOD2-activated MSCs reduced the MC degranulation via NOD2-cyclooxygenase-2 signaling. In contrast to bone marrow-derived MSCs, hUCB-MSCs exerted a cell-to-cell contact-independent suppressive effect on MC degranulation through the higher production of prostaglandin E-2 (PGE(2)). Additionally, transforming growth factor (TGF)-1 production from hUCB-MSCs in response to interleukin-4 contributed to the attenuation of MC degranulation by downregulating Fc epsilon RI expression in MCs. In conclusion, the subcutaneous application of NOD2-activated hUCB-MSCs can efficiently ameliorate AD, and MSC-derived PGE(2) and TGF-1 are required for the inhibition of MC degranulation. Stem Cells2015;33:1254-1266
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