徳島大学 教育・研究者情報データベース(EDB)

1. 徳島大学.大学院医歯薬学研究部.歯学域.口腔科学部門.基礎歯学系.口腔分子病態学(2015年4月1日〜2025年3月31日)

1. (英) Kurosawa Mie / (日) 黒澤 実愛 / (読) くろさわ みえ

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2. 新垣 理恵子

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3. 山田 安希子

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4. 常松 貴明([徳島大学.大学院医歯薬学研究部.歯学域.口腔科学部門.基礎歯学系.口腔病理学])

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5. 工藤 保誠([徳島大学.大学院医歯薬学研究部.歯学域.口腔科学部門.基礎歯学系.口腔生命科学])

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6. (英) Sprent J

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7. 石丸 直澄

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(英) NF κB2 Controls the Migratory Activity of Memory T Cells by Regulating Expression of CXCR4 in a Mouse Model of Sjögren's Syndrome

(英) Dysregulated chemokine signaling contributes to autoimmune diseases by facilitating aberrant T cell infiltration into target tissues, but the specific chemokines, receptors, and T cell populations remain largely unidentified. The aim of this study was to examine the role of the potent chemokine CXCL12 and its receptor CXCR4 in the T cell autoimmune response, using alymphoplasia (aly)/aly mice, a model of Sjögren's syndrome (SS). T cell phenotypes in the salivary gland of aly/aly mice were evaluated using immunologic analysis. An in vitro migration assay was used to assess T cell migratory activity toward several chemokines. Gene expression of chemokine receptors and transforming growth factor β receptors (TGFβRs) was measured by quantitative reverse transcription-polymerase chain reaction. The CXCR4 antagonist AMD3100 was administered to the aly/aly mice in order to evaluate its suppressive effect on autoimmune lesions. Effector memory T (TEM) cells derived from aly/aly mice demonstrated higher in vitro migratory activity toward CXCL12 than did TEM cells from aly/+ mice. CXCL12 expression was specifically up-regulated in the SS target cells of aly/aly mice. TEM cells from RelB mice, but not Nfkb1 mice, also showed high migratory activity toward CXCL12, implicating a role of the nonclassical RelB/NF-κB2 pathway in the regulation of TEM cell migration. TEM cells from aly/aly mice also overexpressed TGFβR type I (TGFβRI) and TGFβRII. The CXCR4 antagonist AMD3100 suppressed autoimmune lesions in aly/aly mice by reducing TEM cell infiltration. Our results suggest that the RelB/NF-κB2 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 the treatment of autoimmune diseases.

1. (英) Animals
2. (英) Chemokine CXCL12
3. (英) Chemotaxis, Leukocyte
4. (英) Disease Models, Animal
5. (英) Gene Expression Regulation
6. (英) In Vitro Techniques
7. (英) Mice
8. (英) Mice, Knockout
9. (英) NF-kappa B p52 Subunit
10. (英) Receptors, CXCR4
11. (英) Sjogren's Syndrome
12. (英) T-Lymphocytes
13. (英) Transcription Factor RelB

1. (英) Article.ELocationID: 10.1002/art.40230

2. (英) Article.PublicationTypeList.PublicationType: Journal Article

3. (英) Article.PublicationTypeList.PublicationType: Research Support, Non-U.S. Gov't