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.

Curcumin Treatment Suppresses CCR7 Expression and the Differentiation and Migration of Human Circulating Fibrocytes

“…Existing in the peripheral circulation, circulating fibrocytes can be recruited into multiple organs in response to chemokines, and actively contribute to fibrogenesis. It has been proved that circulating fibrocytes play a key role in pulmonary [6,31,32], renal [7,8], skin [7,33], hepatic [7,9] and cardiac [7,11] fibrosis. Consequently, it can be speculated that circulating fibrocytes could be one of the common targets for anti-fibrotic therapy in various organs.…”

Effects of Torilis japonica Extract on DNCB-induced Contact Dermatitis in BALB/c Mice

“…is known as stimulator of inflammation at sites of Th2 inflammation, such as in asthma 44) and plays a role in the pathogenesis of AD 59) . Treatment of TJ downregulated DNCB-induced IL-13 mRNA expression in CD mice (Fig.…”

“…TSLP represents a key molecule at the epithelial cell-dendritic cell (DC) interface to initiate allergic inflammation 44) . To investigate the effect of TJ on the mRNA expression of TSLP, real-time PCR was performed.…”

Modulation of Mast Cell Function by Amino Acids In vitro: A Potential Mechanism of Immunonutrition for Wound Healing.

“…An additional role of mast cells in wound healing might be related to IL-13, which is generally accepted as a T cell-related cytokine. T helper type 2 (Th2) cells are the major source of IL-13, and it activates tissue fibrosis in a variety of diseases by promoting collagen accumulation in fibroblasts and myofibroblasts and regulating inflammation [10][11][12][13][14][15][16].…”