アブストラクト
| Title | 皮膚疾患におけるJAK阻害薬の有用性 |
|---|---|
| Subtitle | 特集 〈Clinical Science〉 JAK阻害薬の新展開 |
| Authors | 吉崎歩 |
| Authors (kana) | |
| Organization | 東京大学大学院医学系研究科・医学部皮膚科学 |
| Journal | 炎症と免疫 |
| Volume | 28 |
| Number | 5 |
| Page | 414-419 |
| Year/Month | 2020 / 9 |
| Article | 報告 |
| Publisher | 先端医学社 |
| Abstract | Janus kinase (JAK) 阻害薬は関節リウマチの治療薬として登場して以降, 皮膚疾患領域においても精力的に開発が進められている. 乾癬やアトピー性皮膚炎をはじめとした慢性炎症性皮膚疾患の病態には, 多種のサイトカインが関わっていることが広く知られている. 多くのサイトカインは機能発現に細胞内のJanus kinase signal transducer and activator of transcription (JAK-STAT) 経路を必要としており, JAK阻害薬がこれらの皮膚疾患に有用であろうことは想像に容易い. 実際, 皮膚疾患に対する, JAK阻害薬を用いた数多くの治験が実施されていることから, 今後, 保険適応を得たJAK阻害薬が皮膚科領域にも登場することが強く予想される. 本稿では, 皮膚疾患のうち, まとまった数の治験が実施され, それによりJAK阻害薬の有効性が示唆されている, アトピー性皮膚炎, 尋常性乾癬, 円形脱毛症, 白斑に焦点を当て, 解説した. |
| Practice | 基礎医学・関連科学 |
| Keywords | 皮膚疾患, JAK阻害薬, サイトカイン, JAK-STAT経路 |
- 全文ダウンロード： 従量制、基本料金制の方共に935円(税込) です。
参考文献
- 1) Jatiani SS et al : JAK/STAT pathways in cyto-kine signaling and myeloproliferative disor-ders : approaches for targeted therapies. Genes Cancer 1 : 979-993, 2010
- 2) Damsky W et al : JAK inhibitors in dermatol-ogy : The promise of a new drug class. J Am Acad Dermatol 76 : 736-744, 2017
- 3) Yamaoka K et al : The Janus kinases(Jaks). Genome Biol 5 : 253, 2004
- 4) Ivashkiv LB et al : Signaling by STATs. Arthritis Res Ther 6 : 159-168, 2004
- 5) Hodge JA et al : The mechanism of action of tofacitinib-an oral Janus kinase inhibitor for the treatment of rheumatoid arthritis. Clin Exp Rheumatol 34 : 318-328, 2016
残りの30件を表示する
- 6) Howell MD et al : Targeting the Janus kinase family in autoimmune skin diseases. Front Immunol 10 : 2342, 2019
- 7) Solimani F et al : Emerging topical and systemic JAK inhibitors in dermatology. Front Immunol 10 : 2847, 2019
- 8) Wuthrich B et al : The atopic eczema/dermatitis syndrome. Epidemiology, natural course, and immunology of the IgE associated ("extrinsic") and the nonallergic ("intrinsic"). AEDS. J Inves-tig Allergol Clin Immunol 13 : 1-5, 2003
- 9) Zuberbier T et al : Patient perspectives on the management of atopic dermatitis. J Allergy Clin Immunol 118 : 226-232, 2006
- 10) Thyssen JP et al : Atopic dermatitis is associated with anxiety, depression, and suicidal ideation, but not with psychiatric hospitalization or sui-cide. Allergy 73 : 214-220, 2018
- 11) Neis MM et al : Enhanced expression levels of IL-31 correlate with IL-4 and IL-13 in atopic and allergic contact dermatitis. J Allergy Clin Immunol 118 : 930-937, 2006
- 12) Klonowska J et al : New cytokines in the patho-genesis of atopic dermatitis-new therapeutic targets. Int J Mol Sci 19 : E3086, 2018
- 13) Kim BE et al : Loricrin and involucrin expression is down-regulated by Th2 cytokines through STAT-6. Clin Immunol 126 : 332-337, 2008
- 14) Jin W et al : Topical application of JAK1/JAK2 inhibitor momelotinib exhibits significant anti-inflammatory responses in DNCB-induced atopic dermatitis model mice. Int J Mol Sci 19 : 3973, 2018
- 15) Boniface K et al : IL-22 inhibits epidermal dif-ferentiation and induces proinflammatory gene expression and migration of human keratino-cytes. J Immunol 174 : 3695-3702, 2005
- 16) Nakagawa H et al : Delgocitinib ointment, a topi-cal janus kinase inhibitor, in adult patients with moderate to severe atopic dermatitis : a phase 3, rondomized, double-blind, vehicle-controlled study and an open-label, long-term extension study. J Am Acad Dermatol 82 : 823-831, 2020
- 17) 中村晃一朗ほか : デルゴシチニブ軟膏(コレクチム軟膏 0.5%)安全使用マニュアル. 日皮会誌 130 : 1581-1588, 2020
- 18) Nestle FO et al : Psoriasis. N Engl JMed 361 : 496-509, 2009
- 19) Ito T et al : Epidemiological survey from 2009 t0 2012 of psoriatic patients in Japanese society for psoriasis research. J Dermatol 45 : 293-301, 2018
- 20) Afzali B et al : The role of T helper 17(Th17) and regulatory T cells(Treg) in human organ trans-plantation and autoimmune disease. Clin Exp Immunol 148 : 32-46, 2007
- 21) Lee E et al : Increased expression of interleukin 23 p19 and p40 in lesional skin of patients with psoriasis vulgaris. J Exp Med 199 : 125-130, 2004
- 22) Zheng Y et al : Interleukin-22, a T(h) 17 cyto-kine, mediates IL-23-induced dermal inflamma-tion and acanthosis. Nature 445 : 648-651, 2007
- 23) Wei L et al : IL-21 is produced by Th17 cells and drives IL-17 production in a STAT3-dependent manner. J Biol Chem 282 : 34605-34610, 2007
- 24) Nada HR et al : Expression of Janus Kinase 1 in vitiligo and psoriasis before and after narrow band UVB : a case-control study. Arch Dermatol Res 310 : 39-46, 2018
- 25) Strazzulla LC et al : Alopecia areata : Disease characteristics, clinical evaluation, and new per-spectives on pathogenesis. J Am Acad Dermatol 78 : 1-12, 2018
- 26) Paus R et al : A 'hairy' privilege. Trends Immu-nol 26 : 32-40, 2005
- 27) Craiglow BG et al : Killing two birds with one stone : oral tofacitinib reverses alopecia univer-salis in a patient with plaque psoriasis. J Invest Dermatol 134 : 2988-2990, 2014
- 28) Xing L et al : Alopecia areata is driven by cyto-toxic T lymphocytes and is reversed by JAK inhibition. Nat Med 20 : 1043-1049, 2014
- 29) O'shea JJ et al : JAK and STAT signaling mole-cules in immunoregulation and immune-medi-ated disease. Immunity 36 : 542-550, 2012
- 30) Kruger C et al : A review of the worldwide prevalence of vitiligo in children/adolescents and adults. Int J Dermatol 51 : 1206-1212, 2012
- 31) Van Den Boorn JG et al : Autoimmune destruc-tion of skin melanocytes by perilesional T cells fromvitiligo patients. J Invest Dermatol 129 : 2220-2232, 2009
- 32) Rashighi M et al : CXCL10 is critical for the pro-gression and maintenance of depigmentation in a mouse model of vitiligo. Sci Transl Med 6 : 223ra223, 2014
- 33) Harris JE et al : Rapid skin repigmentation on oral ruxolitinib in a patient with coexistent vitil-igo and alopecia areata(AA). J Am Acad Der-matol 74 : 370-371, 2016
- 34) Craiglow BG et al : Tofacitinib citrate for the treatment of vitiligo : a pathogenesis-directed therapy. JAMA Dermatol 151 : 1110-1112, 2015
- 35) Kim SR et al : Rapid repigmentation of vitiligo using tofacitinib plus low-dose, narrowband UV-B phototherapy. JAMA Dermatol 154 : 370-371, 2018
