Role of profibrogenic cytokines secreted by T cells in fibrotic processes in scleroderma

IL-4 is potentially a major profibrogenic cytokine upregulating the expression of collagen genes. In vivo studies have shown that the disruption of STAT6, IL-4R, IL-4 or transforming growth factor-β (TGF-β) genes in TSK mice, which develop scleroderma-like syndrome, prevented the occurrence of skin sclerosis and of autoantibodies. Additionally, it is known that the homozygosity of TSK mutation is lethal and the embryos die by day 7–8 of pregnancy. The disruption of IL-4 gene rescued from death TSK/TSK mice suggesting a role for IL-4 in embryonic development. Since TGF-β should compensate the lack of IL-4 on regulation of collagen gene expression, we have studied the effect of IL-4 on the expression of TGF-β gene. Our results showed IL-4 dependence of the transcription of TGF-β gene and that in both TSK/+ and TSK/TSK IL-4−/− mice the expression of TGF-β gene is impaired.