Mechanisms of abnormal lamellar body secretion and the dysfunctional skin barrier in patients with atopic dermatitis.
Mechanisms of abnormal lamellar body secretion and the dysfunctional skin barrier in patients with atopic dermatitis.
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DOI：
10.1016/j.jaci.2014.05.048
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发表时间：
2014-10
影响因子：
14.2
通讯作者：
Wakefield, Joan S.
中科院分区：
文献类型：
--
作者：
Elias, Peter M.;Wakefield, Joan S.
关键词：
我们在此回顾表皮结构和酶蛋白的多种遗传性和后天性异常如何汇聚在一起，从而在 AD 中产生有缺陷的渗透性屏障功能和抗菌防御。尽管最为人所知的是聚丝蛋白 (FLG) 突变，但融合 S-100 蛋白家族其他成员（即霍纳蛋白 [hrn] 和聚丝蛋白 2 [flg-2]）的突变；角质化包膜前体（例如 SPRR3）； mattrin，由 Tmem79 编码，调节层状体的组装； SPINK5，编码丝氨酸蛋白酶抑制剂 LEKTI1；脂肪酸转运蛋白 FATP4 都与 AD 相关。然而，这些异常通常只会诱发AD；进一步损害屏障功能的额外后天应激源；例如，心理压力、低环境湿度或高 pH 值表面活性剂通常是引发疾病的必要因素。 Th2 细胞因子还可以通过下调多种表皮结构蛋白、脂质合成酶和抗菌肽的表达来损害屏障功能。所有这些遗传性和获得性异常都集中在层状体分泌系统上，导致脂质成分、分泌和/或细胞外层状膜组织以及抗菌防御异常。最后，我们简要回顾了针对这种新致病模式的治疗方案。
We review here how diverse inherited and acquired abnormalities in epidermal structural and enzymatic proteins converge to produce defective permeability barrier function and antimicrobial defense in AD. Although best known are mutations in filaggrin (FLG), mutations in other member of the fused S-100 family of proteins (i.e., hornerin [hrn] and filaggrin 2 [flg-2]); the cornified envelope precursor (e.g., SPRR3); mattrin, encoded by Tmem79, which regulates the assembly of lamellar bodies; SPINK5, which encodes the serine protease inhibitor, LEKTI1; and the fatty acid transporter, FATP4, have all been linked to AD. Yet, these abnormalities often only predispose to AD; additional acquired stressors that further compromise barrier function; e.g., psychological stress, a low ambient humidity, or high pH surfactants, often are required to trigger disease. Th2 cytokines can also compromise barrier function by downregulating expression of multiple epidermal structural proteins, lipid synthetic enzymes and antimicrobial peptides. All of these inherited and acquired abnormalities converge on the lamellar body secretory system, producing abnormalities in lipid composition, secretion and/or extracellular lamellar membrane organization, as well as in antimicrobial defense. Finally, we briefly review therapeutic options that address this new pathogenic paradigm.
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DOI：
10.1084/jem.20082242
发表时间：
2009-05-11
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Briot A;Deraison C;Lacroix M;Bonnart C;Robin A;Besson C;Dubus P;Hovnanian A
通讯作者：
Hovnanian A
影响因子：
14.2
作者：
De Benedetto, Anna;Rafaels, Nicholas M;McGirt, Laura Y;Ivanov, Andrei I;Georas, Steve N;Cheadle, Chris;Berger, Alan E;Zhang, Kunzhong;Vidyasagar, Sadasivan;Yoshida, Takeshi;Boguniewicz, Mark;Hata, Tissa;Schneider, Lynda C;Hanifin, Jon M;Gallo, Richard L;Novak, Natalija;Weidinger, Stephan;Beaty, Terri H;Leung, Donald Y M;Barnes, Kathleen C;Beck, Lisa A
通讯作者：
Beck, Lisa A
影响因子：
6.5
作者：
Braff, MH;Di Nardo, A;Gallo, RL
通讯作者：
Gallo, RL
DOI：
10.1152/ajpregu.00010.2006
发表时间：
2006-12-01
影响因子：
2.8
作者：
Choi, Eung-Ho;Demerjian, Marianne;Feingold, Kenneth R.
通讯作者：
Feingold, Kenneth R.
影响因子：
6.5
作者：
Choi, EH;Brown, BE;Feingold, KR
通讯作者：
Feingold, KR