Regulation of autoimmune response to Sjogren's syndrome using dental pulp stem cell-derived cytokines

2021 Fiscal Year Final Research Report

• Project/Area Number: 20K23113
• Research Category: Grant-in-Aid for Research Activity Start-up
• Allocation Type: Multi-year Fund
• Review Section: 0907:Oral science and related fields
• Research Institution: Kyushu University
• Principal Investigator: Kawashima Mayu 九州大学, 大学病院, 医員 (90876541)
• Project Period (FY): 2020-09-11 – 2022-03-31
• Keywords: シェーグレン症候群 / サイトカイン / 活性化Tリンパ球抑制 / IL－10 / 制御性T細胞 / TGF-β/ Smad経路

Outline of Final Research Achievements

DPSC-CM contained more secreted factors with tissue-regenerating mechanisms, such as cell proliferation, anti-inflammatory effects, and immunomodulatory effects. DPSC-CM was more effective in suppressing the activated T cells than other groups in the flow cytometric analysis. The stimulated salivary flow rate increased in SS mice with DPSC-CM compared with that in the other groups. In addition, the number of inflammation sites in SMGs of the mice administered with DPSC-CM was lower than that in the other groups. The expression levels of interleukin (Il)-10 and transforming growth factor-β1 were upregulated in the DPSC-CM group, whereas those of Il-4 and Il-17a were downregulated. The DPSC-CM-administered group presented with a significantly increased percentage of regulatory T (Treg) cells and a significantly decreased percentage of type 17 Th (Th17) cells compared with the other groups.

Free Research Field

シェーグレン症候群（自己免疫疾患）

Academic Significance and Societal Importance of the Research Achievements

ヒト歯髄幹細胞培養上清（DPSC-CM）は、顎下腺の唾液分泌機能を促進させる。これは、DPSC-CMが炎症性サイトカインの発現を減少させ、TGF-β/ Smad経路を介して脾臓に制御性T細胞を誘導後、局所的な炎症性微小環境を調節し、顎下腺のアポトーシスを減少させることによって、シェーグレン症候群による唾液分泌低下を抑制する。 DPSC-CMによる活性化T細胞の分化の調節は、この免疫調節機構が関わっている可能性が高い。 したがって、この研究は、DPSC-CMの新しい効果を明らかにし、シェーグレン症候群の新規治療となり得ることを示唆している。