LEAF(TM) Purified anti-human/mouse TGF-beta1

TGF-beta1 is a multifunctional cytokine that plays pivotal roles in diverse biological processes. TGF-beta1 is synthesized as a 390-amino acid precursor that is cleaved by furin, localized in the trans-Golgi network, in the residue 278. Furin processes the TGF-beta1 precursor at the carboxyl side of the consensus sequence RHRR which precedes the NH2-terminal Ala 279 residue of the mature TGF-beta1. The TGF-beta1 precursor includesthe latency-associated peptide (LAP dimer) in the N-terminal portion and the 25 kD portion that constitutes the mature TGF-beta1 in the C-terminal. LAP dimer and the TGF-beta1 mature protein remain non-covalently associated after furin cleavage and this complex does not bind to the TFG-beta1 receptor. In addition, the TGF-beta1 latent complex is joined covalently through LAP to LTBP. The TGF-beta1 active form requires dissociation from LAP. Some activators can release TGF-beta1 from LAP such as thrombospondin-1, reactive oxygen species, and the integrins avb6 and avb8. Mouse TGF-beta1 converts naïve T cells into regulatory T (Treg) cells that prevent autoimmunity. Although human TGF-beta1 is widely used for inducing FOXP3+ in vitro, it might not be an essential factor for human Treg differentiation. Th17 murine can be induced from naïve CD4+ T cells by the combination of TGF-beta1 and IL-6 or IL-21. Nevertheless, the regulation of human Th17 differentiation is distinct. TGF-beta1 seems to have dual effects on human Th17 differentiation in a dose-dependent manner. While TGF-beta1 is required for the expression of RORgt, in human naïve CD4+ T cells from cord blood, TGF-beta1 can inhibit the function of RORgt at high doses. By using serum-free medium, it has been clarified that the optimum conditions for human Th17 differentiation are TGF-beta1, IL-1b, and IL-2 in combination with IL-6, IL-21, or IL-23.