ID 111719
タイトル別表記
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
著者
黒澤, 実愛 徳島大学大学院口腔科学教育部(口腔科学専攻)
Sprent, Jonathan Garvan Institute of Medical Research
キーワード
Sjögren’s Syndrome
dry eye
lacrimal glands
cytokine
chemokine
Autoimmunity
TEM cell
Migration
CXCL12
CXCR4
CXCR7
TGFβ
TGFβR
資料タイプ
学位論文
抄録
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.
掲載誌名
Arthritis & Rheumatology
ISSN
23265205
cat書誌ID
AA12667238
出版者
American College of Rheumatology|Wiley
69
11
開始ページ
2193
終了ページ
2202
発行日
2017-08-13
備考
内容要旨・審査要旨・論文本文の公開
本論文は,著者Mie Kurosawaの学位論文として提出され,学位審査・授与の対象となっている。
権利情報
This is the peer reviewed version of the following article: Kurosawa, M. , Arakaki, R. , Yamada, A. , Tsunematsu, T. , Kudo, Y. , Sprent, J. and Ishimaru, N. (2017), NF‐κB2 Controls the Migratory Activity of Memory T Cells by Regulating Expression of CXCR4 in a Mouse Model of Sjögren's Syndrome. Arthritis Rheumatol, 69: 2193-2202, which has been published in final form at https://doi.org/10.1002/art.40230. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Use of Self-Archived Versions.
EDB ID
出版社版DOI
出版社版URL
フルテキストファイル
言語
eng
著者版フラグ
博士論文全文を含む
文科省報告番号
甲第3174号
学位記番号
甲口第431号
学位授与年月日
2018-03-23
学位名
博士(歯学)
学位授与機関
徳島大学
部局
歯学系
医学系