Recent observations from our group indicate an aberrant TLR responses in SSc that are distinct among patients having lcSSc, ldcSSc and edcSSc. Little is known about the differentiation and maturation of IL17 positive cells in humans. In contrast with the initial reports, we demonstrate that the Th17 phenotype is not confined to CD4+ effector cells but also includes a substantial number of naı ¨ve cells. a-IPM functions as an intermediate during leucine biosynthesis in yeast and activates specifically Leu3p-dependent transcription, both in vivo and in vitro and in mammalian cells. Compared to commonly used inducers tamoxifen and tetracycline that can cause adverse effects during development, a-IPM is an ideal molecular matchmaker since it lacks toxicity, has metabolic stability and lipid solubility. The fact that aIPM functions as an inducer of Leu3p activity in yeast extracts, in mouse pre-adipocytes, in mouse fibroblasts and in double transgenic pMEFs in a range of concentrations with no additional yeast component required for its function demonstrates that a-IPM can act as a safe highly specific ligand. The latter is in line with a recent report investigating Th17 cells in seronegative spondylarthropathy. As explained in this report, potential differences between studies could be explained by slightly differences in isolation protocols. However, an important other explanation might be that the factors that drive Th17 among different diseases differ also with respect to the CD4+ subpopulations that are activated. Taken together, although the underlying mechanisms that explain the distinct patterns of intracellular cytokine expression among SSc phenotypes need to be identified, these patterns suggest distinct immune dysregulation in dcSSc versus lcSSc and in early versus late disease in dcSSc. Recent advances in microfluidic technologies provide new opportunities for cell based assays for clinical research applications, ranging from AIDS diagnostic, to trauma and cancer monitoring. Specifically for chemotaxis applications, after the first reported neutrophil chemotaxis measurements with a microfluidic device, more devices for analyzing neutrophil migration in response to opposing chemoattractant gradients, temporal changes of the gradients, radialy evolving gradients, and overlapping spatial stimuli have been reported. A broad range of applications, from the study of unexpected neutrophil ability to migrate in certain conditions against chemoattractant gradients a.k.a. fugetaxis, to RWJ 64809 side effects practical devices for on-chip isolation of neutrophils from a drop of blood, and testing of new compounds modulators of inflammation response were enabled by the use of microfluidic devices. Unfortunately, while these microfluidic assays have permitted sophisticated experimentation in the laboratory, they are difficult to implement in the clinical setting.