The transcription fac tor of the more recently discovered Th9 subset, producing IL9 cytokine, is still to sellekchem clarify. These cells develop from naive CD4 precursors in response Inhibitors,Modulators,Libraries to TGFB plus IL 4 cytokines. MS is an autoimmune inflammatory demyelinating dis order of the central nervous system. Gender influences both the susceptibility and the clinical course of MS in fact the disease is more common in women than in men and there is an increased proportion of men developing the primary progressive form of MS. The basis for these differences may include immunological factors but the exact mechanism has not yet been established. There is a definite need for more effective biomarkers and therapeutic targets in MS. IFNB therapy is only par tially effective and not in all MS patients.

IFNB therapy can reduce the severity and frequency of relapses, dis ease activity, and disability by inducing mechanisms that determine a fall in sCD30 levels and a re establishment of homeostasis in the Th cell network. On the basis of the above we investigated the possibil ity that sexual dimorphism in autoimmune Inhibitors,Modulators,Libraries diseases could depend on sexual dimorphism in the regulation of Th cell network homeostasis. We carried out studies using the peripheral blood of healthy subjects, IFNB treated and untreated relapsing remitting MS patients, as independent cohorts. We used systems biol ogy to Inhibitors,Modulators,Libraries study APC dependent T cell activation. Cyto kines, sCD30 and EDSS parameters, biomarkers of direction in T cell differentiation and neurological def icit, were used to relate male and female gender to the cytokine pathways regulation of Th cell differentiation.

Methods Experimental design In physiological systems the different components operate as a network Inhibitors,Modulators,Libraries they vary dynamically and co vary each other respectively. Therefore, Inhibitors,Modulators,Libraries the identification of physio logical enough pathways can only be achieved through evaluations of the systems biology characteristics. Due to the complex ity of biological systems, this process requires the use of mathematical models that provide a framework for deter mining the outcome of numerous and simultaneous time dependent and space dependent processes. We designed an experimental approach based on the use of cytokine data driven models of the immune response. All persons gave their informed consent prior to their inclusion in the study. We used the levels of Th cytokines produced by APC as biomarkers of Th cell differentiation the relative proportion of each Th cell type generation depends, in fact, on the relative proportion of specific cytokines produced by APCs and released into the cell environment during resting and activation states of the immune response.