NF-κB2 Controls the Migratory Activity of Memory T Cells by Regulating Expression of CXCR4 in a Mouse Model of Sjögren’s Syndrome

• Material Type: 博士論文
• ISSN: 2326-5205
• Title: NF-κB2 Controls the Migratory Activity of Memory T Cells by Regulating Expression of CXCR4 in a Mouse Model of Sjögren’s Syndrome
• Volume: 69 11
• Author/Editor: Kurosawa, Mie; Arakaki, Rieko; Yamada, Akiko; Tsunematsu, Takaaki; Kudo, Yasusei; Sprent, Jonathan; Ishimaru, Naozumi
• Author Heading: Kurosawa, Mie; Arakaki, Rieko; Yamada, Akiko; Tsunematsu, Takaaki; Kudo, Yasusei; Sprent, Jonathan; Ishimaru, Naozumi
• Publication, Distribution, etc.: American College of Rheumatology|Wiley
• Publication Date: 2017-08-13
• Publication Date (W3CDTF): 2017-08-13
• Alternative Title: シェーグレン症候群モデルマウスにおいて、NF-κB2はCXCR4の発現調節を介してメモリーT細胞の遊走活性を制御する; ROLE OF CXCL12 AND CXCR4 IN A MOUSE MODEL OF SS
• Periodical title: Arthritis & Rheumatology
• Degree grantor/type: 徳島大学
• Date Granted: 2018-03-23
• Date Granted (W3CDTF): 2018-03-23
• Dissertation Number: 甲第3174号
• Degree Type: 博士（歯学）
• Conferring No. (Dissertation): 甲第3174号
• Text Language Code: eng
• Subject Heading: Sjögren’s Syndrome; dry eye; lacrimal glands; cytokine; chemokine; Autoimmunity; TEM cell; Migration; CXCL12; CXCR4; CXCR7; TGFβ; TGFβR
• Target Audience: 一般
• Note (General): Objective. Dysregulated chemokine signaling contributes to autoimmune diseases by facilitating aberrant T-cell infiltration into target tissues, but the specific cytokines, receptors, and T-cell populations remain largely unidentified. Role of the potent chemokine CXCL12 and its receptor CXCR4 in T-cell autoimmune response was examined using alymphoplasia (aly)/aly mice, a Sjögren’s syndrome (SS) model.Methods. T-cell phenotypes in the salivary gland of aly/aly mice were evaluated using immunological analysis. In vitro migration assay was used to assess T-cell migratory activity toward several chemokines. Gene expression of chemokine receptors, and transforming growth factor (TGF)β receptors was measured with quantitative reverse transcription-polymerase chain reaction. The CXCR4 antagonist AMD3100 was administered to the aly/aly mice to evaluate its suppressive effect on autoimmune lesions.Results. Effector memory T (TEM) cells derived from aly/aly mice demonstrated higher in vitro migratory activity toward CXCL12 than aly/+ TEM cells. CXCL12 expression was specifically upregulated in the SS target cells of aly/aly mice. TEM cells from RelB−/− mice, but not nuclear factor (NF)-κB1−/− mice, also showed high migratory activity toward CXCL12, implicating a nonclassical NF-κB2/RelB pathway in the regulation of TEM cell migration. TEM cells from aly/aly mice also overexpressed TGFβ receptors I and II. The CXCR4 antagonist AMD3100 suppressed autoimmune lesions in aly/aly mice by reducing TEM cell infiltration.Conclusion. Our results suggest that the NF-κB2/RelB pathway regulates T-cell migration to autoimmune targets through TGFβ/TGFβR-dependent regulation of CXCL12−CXCR4 signaling. This suggests that these signaling pathways are potential therapeutic targets for treating autoimmune diseases.
• DOI: info:doi/10.1002/art.40230; https://doi.org/info:doi/10.1002/art.40230
• Persistent ID (NDL): info:ndljp/pid/11178430; https://dl.ndl.go.jp/pid/11178430
• Collection: 障害者向け資料
• Collection (Materials For Handicapped People:1): テキストデータ
• Collection (particular): 国立国会図書館デジタルコレクション > デジタル化資料 > 博士論文; https://dl.ndl.go.jp/collections/A00014
• Acquisition Basis: 博士論文（自動収集）
• Date Accepted (W3CDTF): 2018-11-05T10:48:21+09:00
• Format (IMT): application/pdf
• Access Restrictions: 国立国会図書館内限定公開
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• Periodical Title (URI): http://repo.lib.tokushima-u.ac.jp/111719
• Data Provider (Database): 国立国会図書館 : 国立国会図書館デジタルコレクション; https://dl.ndl.go.jp