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-beta (TGF-beta) 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-beta 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-beta gene. Our results showed IL-4 dependence of the transcription of TGF-beta gene and that in both TSK/+ and TSK/TSK IL-4-/- mice the expression of TGF-beta gene is impaired.