lts about the number of circulating Treg cells, the interpretation of the data is problematic. Nevertheless, PubMed ID:http://www.ncbi.nlm.nih.gov/pubmed/19719889 compelling evidence has emerged about the impaired function of these cells in RA patients. Recent investigations revealed that a potentiation of Treg cells is beneficial in RA. In this study we report that the treatment with GXMGal induces strong and TG100 115 web long-lasting increase of FOXP3 expression in RA Treg cells still evident 18 h after stimulation. This was accompanied by early and transient enhancement of GXMGal Improves Treg Function in RA CD4+CD252FOXP3+ fraction of the Treg cell population. Indeed, we found that the anti-inflammatory effects of GXMGal on T cells from RA were quite similar to that observed for MTX. GXMGal differed from MTX just in a few effects, such as increased production of IL-10 in atypical Treg. The fact that GXMGal retains multiple regulatory effects similar to that of MTX and anti-TNF-a agents suggests that GXMGal treatment may provide the combined beneficial effects of MTX and antiTNF-a. Recently, we demonstrated that GXMGal inhibits Th17 activation from RA patients and in the present study we confirm and extend our previously published data by demonstrating that the inhibition of Th17 was related to the inhibition of cytokines such as IL-21, IL-22 and IL-23. Moreover, we also provide evidence that in peripheral T cells from RA, GXMGal inhibits Th1 differentiation in terms of T-bet expression and IL12p70 and IFN-c production. Therefore, the demonstration of a Th1-cell suppression combined with a Th17-cell down-regulation reinforces the idea 
of a possible therapeutic use of GXMGal in RA and other inflammatory chronic disorders. GXMGal-treated Treg cells showed increased suppressive activity manifested by marked inhibition of effector T-cell proliferation. It is known that the total Treg cell pool contains a population of CD45RA+ and CD45RO+ Treg cells. CD45RA+ PubMed ID:http://www.ncbi.nlm.nih.gov/pubmed/19717794 Treg cells were found to be less proliferative than their CD45RO+ counterparts. In multiple sclerosis an impairment of suppressive activity of naive CD45RA+ Treg cells was reported, thereby suggesting that this population may be involved in the pathogenesis of autoimmune disorders. GXMGal is able to bind to CD45RA and CD45RO isoforms and we recently suggested that activated T cells expressing the CD45RO molecule could be the main target of GXMGal-induced apoptosis. Since the Treg population circulating in RA belongs to resting CD45RA phenotype, it is conceivable that GXMGal binds to these cells and increases their function without inducing apoptosis. Therefore these results suggest that in RA patients GXMGal affects Treg function in a two ways: indirectly by inhibition of inflammatory T cells differentiation such as Th1 and Th17 and directly by binding to CD45RA improving activity of Treg. In this study the effect of GXMGal was specifically observed on Treg population as demonstrated by: i) enhanced production of TGF-b1, ii) increased expression of FOXP3 and iii) improved suppression activity on effector T cells. Future studies will be devoted to evaluate the effect of GXMGal in an in vivo experimental model of rheumatoid arthritis. Collectively these data highlight the potential for using GXMGal to enhance Treg activity, inactivate pathogenic T cells and halt the disease process in autoimmunity. Statin is a commonly prescribed drug to lower blood lipid levels and reduce cardiovascular risks via inhibition of the HMG-CoA reductase pathway. It was a