title: Human umbilical cord blood mesenchymal stem cell-derived PGE2 and TGF-β1 alleviate atopic dermatitis by reducing mast cell degranulation.
abstract: 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. Naïve 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 β-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 E2 (PGE2 ). Additionally, transforming growth factor (TGF)-β1 production from hUCB-MSCs in response to interleukin-4 contributed to the attenuation of MC degranulation by downregulating FcεRI expression in MCs. In conclusion, the subcutaneous application of NOD2-activated hUCB-MSCs can efficiently ameliorate AD, and MSC-derived PGE2 and TGF-β1 are required for the inhibition of MC degranulation.
authors.affiliation: Adult Stem Cell Research Center, College of Veterinary Medicine#406 Biotechnology Incubating Center, Seoul National University, Seoul, South Korea; Institute for Stem Cell and Regenerative Medicine in Kangstem Biotech, #406 Biotechnology Incubating Center, Seoul National University, Seoul, South Korea.
authors.forename: Hyung-Sik
authors.initials: HS
authors.lastname: Kim
authors.forename: Jun-Won
authors.initials: JW
authors.lastname: Yun
authors.forename: Tae-Hoon
authors.initials: TH
authors.lastname: Shin
authors.forename: Sung-Hoon
authors.initials: SH
authors.lastname: Lee
authors.forename: Byung-Chul
authors.initials: BC
authors.lastname: Lee
authors.forename: Kyung-Rok
authors.initials: KR
authors.lastname: Yu
authors.forename: Yoojin
authors.initials: Y
authors.lastname: Seo
authors.forename: Seunghee
authors.initials: S
authors.lastname: Lee
authors.forename: Tae-Wook
authors.initials: TW
authors.lastname: Kang
authors.forename: Soon Won
authors.initials: SW
authors.lastname: Choi
authors.forename: Kwang-Won
authors.initials: KW
authors.lastname: Seo
authors.forename: Kyung-Sun
authors.initials: KS
authors.lastname: Kang
mesh_terms: D000818:Animals; D015550:Cell Degranulation / Q000502:physiology*; D002478:Cells, Cultured; D003876:Dermatitis, Atopic / Q000378:metabolism*; D015232:Dinoprostone / Q000096:biosynthesis*; D061307:Human Umbilical Vein Endothelial Cells / Q000378:metabolism / Q000637:transplantation; D006801:Humans; D007279:Injections, Subcutaneous; D008407:Mast Cells / Q000502:physiology*; D045164:Mesenchymal Stem Cell Transplantation / Q000379:methods*; D059630:Mesenchymal Stem Cells / Q000378:metabolism*; D051379:Mice; D053773:Transforming Growth Factor beta1 / Q000096:biosynthesis*
chemical_list: D053773:Transforming Growth Factor beta1; D015232:Dinoprostone
keywords: Atopic dermatitis; Immunomodulation; Mast cell degranulation; Mesenchymal stem cells; NOD2