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犬の炎症性角化異常におけるT細胞サブセットに関する研究

秋山, 智 岐阜大学

2020.03.13

概要

犬の角化異常は, 鱗屑を特徴とする疾患群である。本疾患群は続発性角化異常と原発性角化異常に分類され, さらに,原発性角化異常は炎症を伴う炎症性角化異常と非炎症性角化異常に分類される。犬の炎症性角化異常に類似する疾患として, 人の乾癬がある。人の乾癬では, 17 型ヘルパーT (Th17)細胞が産生するインターロイキン(IL)-17A がケラチノサイトにおける好中球遊走因子の産生を誘導し, 病変部に好中球を遊走させる。また, Th17 細胞が産生する IL-22 はケラチノサイトの増殖亢進および分化異常を引き起こす。その結果, 重度の表皮肥厚および錯角化などの角化異常が生じることから, Th17 細胞は乾癬の病態において重要な役割を果たすと考えられている。一方, 犬の炎症性角化異常の臨床および病理学的特徴はこれまで詳細に解析されておらず, その病態は不明である。本研究では, 犬の炎症性角化異常の病態を明らかにすることを目的として以下の実験を行った。第 1 章では, 犬の炎症性角化異常の臨床および病理学的特徴を調査した。その結果,犬 の炎症性角化異常の皮疹は主に腹部および背部に分布しており, 病理組織学的所見においては, リンパ球および好中球を主体とした炎症細胞の浸潤, 重度な表皮の肥厚および角化亢進が特徴であることが明らかになった。また, すべての症例において,寛解維持にグルココルチコイドまたはシクロスポリン A の投与が必要であった。これらの結果から, 犬の炎症性角化異常の病態における T 細胞の関与が示唆された。

第 2 章では, 犬の炎症性角化異常に関与する T 細胞サブセットを明らかにすることを目的として, 病変部におけるサイトカイン, ケモカイン受容体およびケモカインの遺伝子転写量の解析を実施した。その結果, Th17 サイトカイン, Th17 細胞に選択的に発現しているケモカイン受容体, そのリガンドであるケモカインおよび好中球遊走因子の遺伝子転写量が健常犬の皮膚と比較して増加していることが明らかになった。これらの結果から, 病変部に Th17 細胞が浸潤し, Th17 細胞とケラチノサイトの相互作用により角化異常が生じる病態が推測された。

第 3 章では, 健常犬の末梢血 Th17 細胞割合の加齢変化をフローサイトメトリーにより評価し, その後に炎症性角化異常の犬と比較した。その結果, 健常犬の末梢血 Th17 細胞の割合は加齢とともに増加し, さらに, 犬の炎症性角化異常においては,末梢血 Th17 細胞の割合が健常犬の同年齢対照群と比較して減少していることが明らかになった。したがって, 犬の炎症性角化異常の症例では, 末梢血 Th17 細胞が病変部に遊走する結果, 末梢血 Th17 細胞の割合が減少している可能性が示された。

以上の研究結果から, 犬の炎症性角化異常においては Th17 細胞が病態に関与している可能性が示された。本研究の結果は, Th17 細胞が犬の炎症性角化異常における重症度マーカーあるいは治療標的細胞となり得る可能性を示している。

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