Editorial: Closing in on the Role of Thymic Stromal Lymphopoietin Inhibition as a Therapeutic Entry Point for Systemic Sclerosis

Thymic Stromal Lymphopoietin in Cutaneous Immune-Mediated Diseases

“…They demonstrated specific noticeable perivascular staining attributed to CD163+ macrophages and a few CD4+ and CD8+ T cells ( 91 ). The conflicting results may be ascribed to the specific study sources, and the disease phases since the infiltration of immune cells is commonly observed in the early stage of SSc ( 96 ). Furthermore, Truchetet et al showed that TSLP expression is elevated in the epidermis and dermis of SSc patients.…”

“…Currently, the mechanisms underlying the triggers driving the expression of TSLP in SSc remain unknown. Toll-like receptors (TLR), IL-13, interferons, and TNF superfamily member LIGHT, have been demonstrated to induce TSLP release in SSc ( 96 , 97 ). TLR activation, particularly TLR-3 triggering, induced TSLP expression by fibroblasts in vitro ( 92 ) and poly(I-C), a TLR-3 ligand, was confirmed to induce TSLP expression in infiltrating immune cells in a SSc murine model ( 91 ).…”

“…The profibrotic profile in fibroblasts was consistent with the profibrotic gene signature previously identified in the mouse model by Christmann et al ( 91 ). Moreover, TSLP-activated fibroblasts are capable of producing TGF-β, hence inducing TSLP, leading to a self-amplifying loop ( 96 ). Given the critical role of TSLP in the early phases (endothelial injury and autoimmune inflammation) and late phases (fibrosis) of SSc, therapeutically targeted modulation of TSLP may represent a novel antifibrotic strategy in SSc patients and warrants further investigation.…”