a novel inhibitory cytokine, a member of IL-12 family, which is comprised of Ebi3 (IL-27β) and IL-12a/p35 (IL-12β). Ebi3 gene was found in mean 27% of our samples. Our results are in contrast with Bardel et al. , who did not detected Ebi3 in human T regulatory cells. IL-27 can promote both anti- and pro-inflammatory immune responses (reviewed in ). It has inhibitory effect on Th1, Th2 and Th17 subpopulations, but it also inhibits the development of Tregs via the influence on STAT3 . The diminished IL-27 expression in Tregs found in our study could also confirm the role of this cytokine in disturbances of immune balance observed in the MS. The production of TGF-β by Tregs is involved in their regulatory activity Selleck Neratinib in intestinal inflammation and diabetes
[31, 32]. However, some data demonstrate that in inflammatory bowel disease, Treg-mediated suppression is not TGF-β1 dependent . Thus, a diminished TGF-β expression in Tregs can lead to the appearance of low-grade inflammatory process accompanying MS. In our samples, the expression of TGF-β receptors was only a little bit different between study and control group. One of the cytokines with multifarious functions is interferon gamma. Usually regarded as proinflammatory cytokine, it is also produced by Tregs and plays some role in their activation (discussed in ). The immunoregulatory role of FoxP3+/IFN-γ+ cells was Selleck Vemurafenib confirmed in patients after kidney transplantation . The reduced expression of this cytokine in Tregs separated from children with MS could indicate the EGFR inhibitor dysfunction of these cells. ICOS, GITR, CTLA-4, 4-1BB and OX40 belong to the most important molecules in keeping proper Treg function. We found only minimal changes in the expression of ICOS, GITR and CTLA-4, but the amounts mRNA for 4-1BB and OX40 were higher in
Tregs separated from children with MS when compared to reference children. CTLA-4 controls T regulatory cells’ function and is required for the suppression of autoimmune response in diabetes . ICOS contributes to the role of Tregs in the pathogenesis of atherosclerosis, but its role in obesity and MS is not yet elucidated . Although the signalling of TNF receptor family members, OX40/4-1BB seems to be important for Treg function, their role is largely unknown. OX40 is regarded as negative regulator of FoxP3 and antagonizer of Tregs . In contrast to our findings, Liu et al. found decreased 4-1BB expression on Tregs in patients with multiple sclerosis . It is possible that 4-1BB and OX40 regulate Treg function in both positive and negative manners (reviewed in ). The cytotoxic activity of T regulatory cells is contentious. In our samples (both study and control groups), we didn’t find any mRNA for granzyme A. This confirms our previous findings, and other authors usually examined granzyme B expression in Tregs [41, 42]. In contrast, Grossman et al.