title: IL-13 induces skin fibrosis in atopic dermatitis by thymic stromal lymphopoietin.
abstract: Skin fibrotic remodeling is a major feature in human atopic dermatitis (AD). Inflammation and tissue fibrosis are common consequences of Th2 responses. Elevated IL-13 and thymic stromal lymphopoietin (TSLP) have been found in the AD skin lesions. Fibrocytes can be recruited to inflamed tissues to promote wound healing and fibrosis. Dermal transgenic expression of IL-13 causes an AD-like phenotype with fibrosis and increased TSLP. However, the role of TSLP in fibrotic remodeling is unknown. In this study, we investigated the role of TSLP and fibrocytes in the generation of IL-13-induced skin fibrosis. In AD lesion, cessation of IL-13 transgene expression resulted in reduced skin inflammation but with no effect on further progression of fibrosis. This was accompanied by markedly increased CD34(+)/procollagen 1(+) fibrocytes. Furthermore, fibrocytes express TSLP receptor (TSLPR), and TSLP directly promotes PBMC-derived fibrocytes to produce collagen. Neutralization of TSLP or genetic deletion of TSLPR in IL-13 transgenic mice resulted in a significant reduction in fibrocytes and in skin fibrosis. Furthermore, reduction of fibrosis by depletion of TSLP was independent of IL-13. Interestingly, the number of fibrocytes was highly increased in the skin samples of AD patients. These data indicate that the progression of skin fibrosis in IL-13-induced AD occurs via TSLP/TSLPR-dependent but IL-13-independent novel mechanisms by promoting fibrocyte functions.
authors.affiliation: Division of Allergy and Clinical Immunology, Department of Medicine, The Johns Hopkins University School of Medicine, Baltimore, MD 21224, USA.
authors.forename: Min-Hee
authors.initials: MH
authors.lastname: Oh
authors.forename: Sun Young
authors.initials: SY
authors.lastname: Oh
authors.forename: Jinho
authors.initials: J
authors.lastname: Yu
authors.forename: Allen C
authors.initials: AC
authors.lastname: Myers
authors.forename: Warren J
authors.initials: WJ
authors.lastname: Leonard
authors.forename: Yong Jun
authors.initials: YJ
authors.lastname: Liu
authors.forename: Zhou
authors.initials: Z
authors.lastname: Zhu
authors.forename: Tao
authors.initials: T
authors.lastname: Zheng
mesh_terms: D000818:Animals; D016207:Cytokines / Q000502:physiology*; D003876:Dermatitis, Atopic / Q000473:pathology*; D018450:Disease Progression; D005355:Fibrosis / Q000209:etiology*; D006801:Humans; D018793:Interleukin-13 / Q000235:genetics / Q000502:physiology*; D051379:Mice; D008822:Mice, Transgenic; D019076:Transgenes; D000094632:Thymic Stromal Lymphopoietin
chemical_list: D016207:Cytokines; D018793:Interleukin-13; D000094632:Thymic Stromal Lymphopoietin