皮膚の免疫・アレルギー (アレルギー免疫治療の最新の進歩)

機関リポジトリ

書誌事項

タイトル別名
  • Allergy and Immune Response in the Skin
  • ヒフ ノ メンエキ アレルギー トクシュウ アレルギー メンエキ チリョウ ノ サイシンノ シンポ

この論文をさがす

抄録

type:特集

アトピー性皮膚炎の病態理解の歴史を振り返り,最新の知見と対比させて紹介した.皮膚の乾燥,湿疹,強い掻痒,高IgE 値などを特徴とし,喘息やアレルギー性鼻炎などを合併しやすい疾患であるとの古典的な理解は現在も変わらない.最も大きく変化したのは「皮膚の乾燥」の意義である.フィラグリンの異常などに伴う皮膚バリア異常が蛋白抗原による経皮感作を容易にし,食物アレルギー,ダニアレルギー等が誘導される.皮膚バリア障害によって誘導されるthymic stromal lymphopoietin( TSLP)がIgE産生や抗原特異的,非特異的なTh2 サイトカイン産生リンパ球を誘導し,掻痒にも関連する.つまり,表皮の異常により一元的にアトピー性皮膚炎の病態が説明できるようになったと言える.誘導されたTh2 タイプの炎症は皮膚バリア異常を誘導し,線維芽細胞にペリオスチンの産生を促し,さらに表皮細胞にTSLP の産生を誘導する.また,末梢神経や神経ペプチドによる神経原性炎症は炎症の増幅,掻痒閾値の低下,皮膚バリア異常を誘導する.この様に主要な病態が相互に影響し合うこともアトピー性皮膚炎の特徴的な病態といえる.

Pathogenesis of atopic dermatitis( AD) has been complex and difficult to understand for many years, because not only allergic and immune response but also the function of residual cells:keratinocytes, fibroblasts and peripheral nerve, are involved in inflammation and itch of atopic dermatitis. Discover of frequent filaggrin gene loss-of-function mutations in patients with AD in 2006 have changed the concept of pathogenesis of AD. Disruption of cutaneous permeability barrier function due to loss-of-function of filaggrin gene or other induces not only Th2 type immune response in the skin but also in lung as asthma and food allergy by induction of thymic stromal lymphopoietin (TSLP). TSLP also directly induces itch, and induces type 2 innate lymphoid cells in corporate with IL-33 and IL-25 produced by keratinocytes as well as TSLP without specific antigens. Thus excessive production of TSLP following barrier dysfunction is considered to play a central role for AD. In addition to permeability barrier dysfunction, pruritus and Th2-dominant conditions are the most important characteristics of AD. Pruritus may be caused by IL-31 produced by Th2 or induced by penetrating peripheral nerve into epidermis following barrier disruption. Th2-dominant environments induce barrier dysfunction, reduced levels of anti-microbial peptides, and increased synthesis of periostin by fibroblasts followed by TSLP production by keratinocytes, which maintains and exacerbates AD. Neurogenic inflammation induced by neuropeptides such as substance P enhances inflammation, weakens permeability barrier function functionally and mechanically, and lowers threshold of itch. Thus barrier dysfunction, pruritus, and Th2 condition are established as major three characteristics of AD and their mutual effects make AD complicated. Based on the pathogenesis of AD, new therapeutic approaches have started: proactive therapy to stop a vicious itch-scratch spiral and intensive treatment with moisturizer for infant to prevent from development of AD.

identifier:12

identifier:KJ00009545209

収録刊行物

キーワード

詳細情報 詳細情報について

問題の指摘

ページトップへ