Elucidation of mechanism underlying intrinsic atopic dermatitis induced by deficiency of sprabasin co-expressed in skin and intestine
| Project/Area Number |
17H04241
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (B)
|
| Allocation Type | Single-year Grants |
|---|
| Section | 一般 |
|---|
| Research Field |
Dermatology
|
|---|
| Research Institution | Hamamatsu University School of Medicine |
|---|
Principal Investigator |
Tokura Yoshiki 浜松医科大学, 医学部, 特任教授 (00172156)
|
|---|
| Project Period (FY) |
2017-04-01 – 2020-03-31
|
| Project Status |
Completed (Fiscal Year 2020)
|
| Budget Amount *help |
¥12,090,000 (Direct Cost: ¥9,300,000、Indirect Cost: ¥2,790,000)
Fiscal Year 2019: ¥3,380,000 (Direct Cost: ¥2,600,000、Indirect Cost: ¥780,000)
Fiscal Year 2018: ¥3,380,000 (Direct Cost: ¥2,600,000、Indirect Cost: ¥780,000)
Fiscal Year 2017: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000)
|
|---|
| Keywords | 皮膚科学 / 炎症学 / アレルギー / 免疫学 / 皮膚免疫 |
|---|
| Outline of Final Research Achievements |
Suprabasin (SBSN) is expressed in epidermis and epithelial cells of the upper digestive tract where metals such as nickel are absorbed. SBSN level was decreased in the stratum corneum and serum of atopic dermatitis (AD) patients, especially in intrinsic AD, which is characterized by metal allergy. By using SBSN-null (Sbsn-/-) mice, we investigated the outcome of SBSN deficiency. Sbsn-/- mice exhibited skin barrier dysfunction on embryo, but after birth, their barrier function was not perturbed. Sbsn-/- mice showed rather lower contact hypersensitivity (CHS) responses to haptens than did wild-type mice. The blood nickel (Ni) level after oral feeding of nickel was significantly higher in Sbsn-/- mice, and CHS to Ni was elevated in Sbsn-/- mice under Ni-loading condition. The completely SBSN deficient mice retain normal barrier function, but harbor abnormal upper digestive tract epithelium that promotes Ni absorption and high CHS to nickel, sharing the features of intrinsic AD.
|
| Academic Significance and Societal Importance of the Research Achievements |
学術的意義として、病態が不明の内因性ADの原因の一つに、SBSN欠乏がある可能性を提起した。従来、内因性ADは血清IgE値が高くないサブタイプとして不思議な存在であった。若い女性に多く、どういう訳か金属アレルギーの頻度が高い。バリア機能も損なわれていない。これがSBSN欠乏によってもたらされる場合があることを示唆した。これは社会的意義として、若い女性に多い内因性ADの解明に繋がることにより、患者の不安感を払拭し、将来的な治療の開発に道を開いた。
|
Report
(4 results)
Research Products
(42 results)
-
-
-
-
-
-
-
-
[Journal Article] Confusion in determination of two types of cutaneous adverse reactions to drugs, maculopapular eruption and erythema multiforme, among the experts: A proposal of standardized terminology2020
Author(s)
Hashizume H, Abe R, Azukizawa H, Fujiyama T, Hama N, Mizukawa Y, Morita E, Nakagawa Y, Nakajima S, Niihara H, Teraki Y, Tohyama M, Watanabe H, Tokura Y, Drug Allergy Database Committee in Japanese Cutaneous Immunology and Allergy Association
-
Journal Title
J Dermatol
Volume: 47
Issue: 2
Pages: 169-173
DOI
Related Report
Peer Reviewed
-
-
-
-
-
-
-
-
-
-
-
-
-
[Journal Article] Sensitive skin is highly frequent in extrinsic atopic dermatitis and correlates with disease severity markers but not necessarily with skin barrier impairment.2018
Author(s)
Yatagai T, Shimauchi T, Yamaguchi H, Sakabe J-I, Aoshima M, Ikeya S, Tatsuno K, Fujiyama T, Ito T, Ojima T, Tokura Y:
-
Journal Title
J Dermatol Sci
Volume: 89
Issue: 1
Pages: 33-39
DOI
Related Report
Peer Reviewed
-
[Journal Article] Efficacy and safety of ustekinumab in Japanese patients with severe atopic dermatitis: a randomized, double-blind, placebo-controlled, phase II study.2017
Author(s)
Saeki H, Kabashima K, Tokura Y, Murata Y, Shiraishi A, Tamamura R, Randazzo B, Imanaka K:
-
Journal Title
Br J Dermatol
Volume: 177
Issue: 2
Pages: 419-427
DOI
Related Report
Peer Reviewed
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
