However, it is difficult to assess the specific role of CCL19 inhibition because SFA exerts pleiotropic effects both on chemokine expression and chemokine reponsiveness. Furthermore, CD38 suppression in moDC by SFA may represent only one possible explanation for reduced DC Nilotinib migration but the results do not provide formal evidence for a direct link between CD38 and reduced chemokine expression or responsiveness. Notably, besides migration, CCL19/CCl21 chemokines have been correlated with autoimmunity and immune suppression indicating an important additional role balacing immunity and tolerance. SFA��s effects on CCL5, CCL17, CCL19 and CD38 expression are likely to be independent of cyclophilin-binding since preincubation with a 100-fold molar excess of CsA did not abrogate SFA’s inhibitory effects. These findings are in agreement with Zenke et al., who demonstrated that SFA��s activity in the MLR is not abrogated in the presence of a 10-fold molar excess of the cyclophilin-binding nonimmunosuppressive derivative, 4-Cs. These findings provided additional insight into SFA��s effects to inhibit chronic graft vasculopathy in CsA-treated recipients. Chronic graft vasculopathy is characterized by continuous intimal proliferation and infiltration of leukocytes. The infiltration and activation of leukocytes is mediated by chemokines that are believed to play a critical role in the immunopathology of this process. Suppression of DC chemokine expression and DC migration by SFA is likely to promote SFA’s capacity to inhibit graft vasculopathy. In conclusion, this first systematic genome-wide study revealed a novel anti-inflammatory mode of action of SFA being different from the related agent CsA. The suppressive activity of SFA with regard to DC chemokine expression and migration in addition to its inhibitory effects on DC antigen uptake and DC bioactive IL12 production identifies this immunophilin-binding agent as a novel partner for combination with potent T-cell inhibitors. Furthermore, with respect to the development of novel cell migration inhibitors targeting either chemokine receptors, selectin receptors or integrin receptors, SFA seems to represent an attractive combination partner to potentiate the anti-inflammatory activity of these novel agents. Since this study was focused on the systematic analysis of SFA’s effects on human moDCs, further studies are necessary to analyse the effects of SFA on chemokine expression in T and B lymphocytes. Many enzymes and proteins such as members of the potato proteinase inhibitor II superfamily have disulphide bonds formed between the thiol groups of cysteine residues. Although the amino acid residue methionine also contains sulphur, methionine cannot form disulphide bonds. The disulphide bond, usually formed between different regions or peptides, is relatively strong. Its typical bond dissociation energy is 60 kcal/mole. This is approximately 71% of the strength of a typical peptide backbone carbon-carbon bond. Disulphides perform diverse functions in proteins, from maintaining the folding and stability of proteins to preserving bioactive structure essential to specific ICG-001 protein function. Analysis of naturally occurring variants can reveal insights into the natural selection and evolution of disulphide bond-containing proteins. Disulphide bonds were thought to 
be generally very well conserved in proteins. However, a recent large scale analysis on structural features in homologous protein domain families of known 3-D structures reported that only 54% of disulphide bonds compared between homologous pairs are conserved.