Polarized subsets of human T-helper cells induce distinct patterns of chemokine production by normal and systemic sclerosis dermal fibroblasts

Fibroblasts are cells of mesenchymal origin and are principally involved in the generation and maintenance of extracellular matrix. Fibroblast morphology, phenotype and function may vary depending on the tissue of origin and on whether the tissue is exposed to physiological or pathological conditions. Thus, cultured fibroblasts derived from skin, breast, lung and haematopoietic tissue have been shown to express structural, extracellular matrix and surface proteins differentially, and to produce different cytokines [1-3]. Chemokine production may also vary depending on the source of fibroblasts, and differences in the levels of eotaxin/CC chemokine ligand (CCL)11, IL-8/CXC chemokine ligand (CXCL)8, monocyte chemoattractant protein (MCP)-1/CCL2, RANTES (regulated upon activation normal T cell expressed and secreted)/CCL5, and macrophage inflammatory protein (MIP)-1α/CCL3 have been reported [3]. In addition, production by fibroblasts of chemokines may be variably modulated by cytokines, with differences being related to the origin of the fibroblasts [4-8].Chemokines are soluble mediators that were originally identified because of their chemotactic properties in cells expressing specific receptors. Indeed, chemokines that influence chemotaxis regulate leucocyte homeostasis and recruitment of leucocyte subpopulations at sites of inflammation [9]. However, their biological functions are broader, comprising relevant roles in virus cell entry, angiogenesis, tumour growth, metastasis formation and fibrosis [10]. For instance, MCP-1/CCL2 – a CC chemokine that binds to CC chemokine receptor (CCR)2 – has attracted keen interest in the field of fibrosis because it appears to play direct roles in collagen and matrix metalloproteinase-1 induction on fibroblasts [11-13] and is present at sites undergoing fibrosis. In human systemic sclerosis (SSc), MCP-1 mRNA proved to be the most abundant mRNA when bronchoalveolar lavage cells from SSc lung were compared with controls using microa