The FOXP3 gene (ID: 50943), forkhead box protein 3, a member of transcription factor winged-helix family, is located on chromosome Xp11.23 within the area of AIDs (autoimmune diseases) linkage. It is found that FOXP3 gene is mostly expressed in the CD4
+CD25
+ regulatory T cells (Treg), and the surface expression of FoxP3 in CD4
+CD25
− T cells is adequate to modify them into Treg with significant inhibition activity (Khattri et al.
2003; Hori et al.
2003; Fontenot et al.
2003). The expression of FOXP3 in CD4
+ T cells is related to their possibility to function as regulatory T cells (Walker et al.
2003). The many signals that infer the expression of FOXP3 have been described, but the exact mechanisms by which the expression of this protein is controlled in Treg cells are not well understood. It has been described that the synergistic operation of signals downstream of the T-cell receptor (TCR), costimulatory molecules, and cytokine receptors is required for the inclusion of transcription of FOXP3 (Huehn et al.
2009).
Multiple sclerosis (MS), like many other autoimmune diseases, is thought to consequence from a failure of the regular immune tolerance mechanisms, which correspond to pathogenic T cells directed vs self-antigens. T regulatory cells (CD4
+CD25
+) play an essential role in the inflection of potentially self-reactive T-cell clones, as they significantly inhibit the immune reply of autoreactive T cells (Maloy and Powrie
2001; Sakaguchi et al.
2001). Notwithstanding, identifying evident failure in Treg-mediated immune control in the widespread human autoimmune disorders has been difficult. This may result from the diversity of the phenomenon of human autoimmunity and from the fact that both genetic and environmental factors are responsible for the disease. Furthermore, a lot of research estimated the number of CD4
+CD25
+ and FOXP3
+ T cells in peripheral blood mononuclear cells of patients diagnosed with MS, T1D, and RA, and found no distinctions in the frequency of these cells towards with reference group (Brusko et al.
2005; Cao et al.
2003; Feger et al.
2007; Haas et al.
2005). However, a number of studies showed alterations in the frequency of FOXP3
+ T cells in these disorders. In MS, both an magnification (Kumar et al.
2006) and reduction (Venken et al.
2008) in FOXP3
+ Treg were observed, and in rheumatoid arthritis and newly diagnosed T1D (type 1 diabetes), an increase in FOXP3
+ Treg was found (Han et al.
2008; Marwaha et al.
2010). The Treg cells with reduced mRNA expression of FOXP3 gene have reduced amount of the Treg celldistinctive genes like CTLA4, EBI3, interleukin 10, and ENTPD1, and increase the expression of T effector cytokine genes such as IFN gamma, TNF alfa, interleukins 4 and 17 (Williams and Rudensky
2007; Wan and Flavell
2008; Zhou et al.
2008; Gavin et al.
2007). Mutations or SNP (single nucleotide polymorphism) of FOXP3 gene may modify its role functionally or quantitatively, therefore leading to the absence of functional CD4
+CD25
+ Tregs, resulting in some autoimmune diseases (Wildin et al.
2002), such as immunodysregulation, polyendocrinopathy, enteropathy, X-linked IPEX (immunodysregulation polyendocrinopathy enteropathy) syndrome (Vliet and Nieuwenhuis
2007), type 1 diabetes (T1D) (Bassuny et al.
2003), and autoimmune thyroid diseases (Ban et al.
2007). Polymorphisms have been described in various regions of the FOXP3 gene, such as the promoter, intron, and exon regions. The promoter is highly conserved part of the FOXP3 gene, which is situated 6.5-kb upstream of the first coding exon of FOXP3. This region consists of characteristic TATA and CAAT-box sequences which is activated after NFAT (nuclear factor of activated T lymphocytes) and AP1 (activator protein 1) binding to the TCR receptor (Mantel et al.
2006). Therefore, FOXP3 is an appropriate candidate gene to play a role in organ-specific autoimmune diseases, in particular T1D, thyroid autoimmunity and multiple sclerosis. MS is one of the leading neurodegenerative causes of physical disability. Heterogenetic background of autoimmunity pathway components has been suggested in MS pathogenesis. The purpose of our research was confirm and understand the potential role and relationship of chosen polymorphisms of FOXP3 gene (rs3761549, rs3761548, rs3761547) with different clinical MS data of our relapsing-remitting MS groups of patients and in unrelated group. This is the first study of MS patients in the Eastern part of the Polish population.