Chemokines and chemokine receptors in the pathogenesis of systemic sclerosis

Abstract  Activation of the immune system and increased synthesis of extracellular matrix proteins by fibroblasts are hallmarks in the pathogenesis of systemic sclerosis (SSc). The mechanisms that initiate the accumulation of inflammatory cells are still unknown. Chemokines are a family of small molecules that are divided into subfamilies according to the position of NH2-terminal cysteine motif. A new nomenclature for chemokines recently has been introduced in an attempt to overcome the confusion resulting from a number of different names for the same chemokines. Recent data indicate that chemokines, and in particular MCP-1 (CCL2), might be involved in the pathogenesis of SSc at different levels. MCP-1 is highly upregulated in skin specimens from SSc patients compared with those from healthy controls. Dermal fibroblasts release MCP-1, which is able to induce and perpetuate the migration of inflammatory cells into the skin. Interestingly, data from animal models, as well as from in vitro studies, indicate that MCP-1 might also be involved in the increased synthesis of extracellular matrix proteins, by either direct or indirect mechanisms. In conclusion, chemokines represent interesting candidates for target-directed therapies for SSc. This concept has to be confirmed by further studies using animal models for SSc and other fibrotic diseases.