TSLP Is a Potential Initiator of Collagen Synthesis and an Activator of CXCR4/SDF-1 Axis in Keloid Pathogenesis

Abstract

Recently, thymic stromal lymphopoietin (TSLP), which is well studied in allergic diseases, has been reported in fibrotic diseases, including idiopathic pulmonary fibrosis and atopic dermatitis fibrosis. However, the role of TSLP in keloid is obscure. In this study, we assessed the expression of TSLP in keloid tissue and investigated the possible role of TSLP in keloid pathogenesis. We observed that TSLP expression was increased in keloid tissue compared to normal tissue. Furthermore, TSLP treatment induced increased collagen I and collagen III expression in fibroblasts via transforming growth factor-?; however, there was higher expression in keloid fibroblasts compared to normal fibroblasts. Stromal cell-derived factor-1?, which was recently reported to enhance wound healing through recruiting bone marrow-derived mesenchymal stem cells to the wound area, increased after TSLP treatment in fibroblasts and was primarily expressed in ?-smooth muscle action-positive myofibroblasts in keloid tissue. Furthermore, fibrocytes expressing CXCR4, a stromal cell-derived factor-1? receptor, were significantly increased in keloid tissue compared to normal tissue. Finally, intradermal TSLP injection on BALB/c mice increased stromal cell-derived factor-1? expression and CXCR4(+) fibrocytes infiltration. Our data suggest that TSLP is a potent inducer of collagen and transforming growth factor-? production in keloid fibroblasts. In addition, it might activate the CXCR4/stromal cell-derived factor-1 axis to increase fibrocyte infiltration into the keloid tissue.

TSLP-activated dendritic cells induce human T follicular helper cell differentiation through OX40-ligand

“…TSLP is expressed in a broad spectrum of diseases. This is the case of AD (Soumelis et al, 2002), psoriasis (Volpe et al, 2014), NS (Hovnanian, 2013; Furio and Hovnanian, 2014), keloid (Shin et al, 2016), and helminthic infections (Ramalingam et al, 2009; Ziegler and Artis, 2010; Giacomin et al, 2012). In some of these diseases, Tfh cells have been reported (Glatman Zaretsky et al, 2009; Niu et al, 2015).…”

Characterization of single cell derived cultures of periosteal progenitor cells to ensure the cell quality for clinical application

“…The gene expression for TSLP displayed the highest FC m in undifferentiated tripotent clonal cultures compared cultures that did not comprise chondrogenic differentiation. For keloid firboblasts TSLP is described as a potent inducer of collagen and TGF-β production [19]. Among the other 52 genes with different gene expression is Transforming Growth Factor beta Type III Receptor ( TGFBR3 ).…”

Another Piece in the Fibrotic Puzzle: TSLP as a Novel Ligand for Fibrocyte Activation

“…Our group observed a clear dual effect with proinflammatory and profibrotic signatures in vitro and in vivo (Christmann et al, 2013). Another piece of the puzzle that Shin et al (2016) revealed was that the profibrotic effect of TSLP seems to be dependent on TGF-b, at least in dermal fibroblasts. The question still remains concerning whether TSLP profibrotic effects are TGF-b dependent in vivo, although our unpublished studies are pointing to the same direction.…”

“…Several mechanisms have been proposed to play roles in the development of keloids. Shin et al (2016) report novel pathways that play roles in this complex disease.…”

“…Fibroblasts were reported to produce TSLP, followed by fibroblast CCL2 release and subsequent monocyte chemotaxis. Shin et al (2016) reported the strong expression of TSLP in keloidal tissues, another fibrotic skin disease. With respect to the fibrotic effect of TSLP, our group observed that injection of TSLP into the skin of mice caused upregulation of a cluster of genes, overlapping with IL-13 and transforming growth factor-b (TGF-b).…”