Premium
The T h2 cytokine, interleukin‐4, abrogates the cohesion of normal stratum corneum in mice: implications for pathogenesis of atopic dermatitis
Author(s) -
Hatano Yutaka,
Adachi Yasuko,
Elias Peter M.,
Crumrine Debra,
Sakai Takashi,
Kurahashi Rieko,
Katagiri Kazumoto,
Fujiwara Sakuhei
Publication year - 2013
Publication title -
experimental dermatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.108
H-Index - 96
eISSN - 1600-0625
pISSN - 0906-6705
DOI - 10.1111/exd.12047
Subject(s) - thymic stromal lymphopoietin , stratum corneum , filaggrin , atopic dermatitis , cytokine , immunology , dermoepidermal junction , pathogenesis , interleukin , loricrin , hairless , involucrin , keratinocyte , chemistry , kallikrein , biology , biochemistry , enzyme , anatomy , in vitro , genetics , dermis
There is mounting evidence that T h2 cytokines adversely affect skin barrier functions and contribute to the pathogenesis of atopic dermatitis ( AD ). AD is also characterized by abnormal cohesion in the stratum corneum ( SC ). However, the contribution of T h2 cytokines to this abnormality remains unknown. This study examined the effects of IL ‐4, a prototypic T h2 cytokine, on the cohesion of the SC . Structural and physiological assessments revealed that repeated intradermal injections of IL ‐4 compromised the cohesion of the SC of normal hairless mice. Two potential mechanisms were explored to account for the altered cohesion. First, IL ‐4 decreased the amount of corneodesmosomes and down‐regulated the expression of desmoglein 1, but not of corneodesmosin ( CDSN ) or loricrin expression, in murine skin and in cultured human keratinocytes ( KC ). IL ‐4 did not affect the skin surface p H , and in situ zymography revealed no net change in total serine protease activity in the IL ‐4‐treated SC . Yet, IL ‐4 enhanced expression of kallikrein ( KLK )7, while simultaneously down‐regulating KLK 5 and KLK 14. Finally, IL ‐4 did not alter the expression of the lympho‐epithelial K azal‐type inhibitor ( LEKTI ) in KC . This study suggests that IL ‐4 abrogates the cohesion of SC primarily by reducing epidermal differentiation.