TGF-β plays a very active role in Th2-mediated immune response and tissue remodeling, e.g. it could upregulate IL-13 synthesis through GATA-3 expression in the T lymphocytes of patients with systemic sclerosis [21], while TGF-β signaling defect is linked to methotrexate resistance in rheumatoid arthritis [22]. The gene discussed is TGFB1; the disease is systemic sclerosis.