The Th2 cytokine, interleukin-4, abrogates the cohesion of normal stratum corneum in mice: implications for pathogenesis of atopic dermatitis.

There is mounting evidence that Th2 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 Th2 cytokines to this abnormality remains unknown. This study examined the effects of IL-4, a prototypic Th2 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 KLK5 and KLK14. Finally, IL-4 did not alter the expression of the lympho-epithelial Kazal-type inhibitor ( LEKTI) in KC. This study suggests that IL-4 abrogates the cohesion of SC primarily by reducing epidermal differentiation. [ABSTRACT FROM AUTHOR]