Aim o the study To compare the potential of CD4+CD25C cells, isolated from both healthy rats and rats with CIA (Collagen-Induced Arthritis), for differentiation into regulatory T cells in the presence of all-trans retinoic acid in order to learn more about the activation mechanisms and therapeutic potential of regulatory T cells. with ATRA were also investigated. Results CD4+CD25C cells isolated from healthy animals or from animals with CIA are characterised by different potential of the differentiation into CD4+CD25+ FOXP3+ cells. Retinoic acid receptor Rxr is present in the CD4+CD25C cells isolated from rats with CIA. Conclusions We showed that although ATRA did not increase the frequency of Treg in culture, it significantly increased expression of rar and rxr only in lymphocytes taken from diseased animals and foxp3 expression only in healthy animals. Moreover, after ATRA stimulation, the frequency of Treg-produced IL-10 tended to be lower in diseased animals than in the healthy group. The results imply that the potential of na?ve cell CD4 lymphocytes to differentiate into Tregs and their putative suppressive function is dependent on the donors health status. conditions [1]. The Treg lymphocytes are responsible for peripheral tolerance of self-antigens, and they control the immune response process against exogenous antigens [2]. Their immunosuppressive effect is conditioned by stable expression of the FOXP3 transcription factor and consists C among others C of the release of immunosuppressive cytokines such as IL-10 and TGF-, as well as the reduction of antigen presentation by antigen-presenting cells, by blocking their costimulatory function [3]. Some Tregs can be differentiated from CD4+ in the presence of IL-10 in conditions. These Tregs have been named Treg 1, and their main characteristic feature is high secretion of IL-10. However, it is also possible to obtain Tregs that produce TGF- (named Gdf11 Th3) [4]. Maynards team demonstrated that, despite Guanabenz acetate IC50 the induction of Foxp3 by TGF-, ATRA in the signal path of TGF- inhibits the secretion of IL-10 in CD4+ naive cells. Similarly, ATRA produced in the small intestine by dendritic cells inhibits induction of IL-10 in CD4+ cells but initiates the expression of Foxp3. In their studies, they also made the control cell cultures of CD4+ T cells in the presence of a RAR antagonist C LE540, which resulted in secretion of IL-10 at a level significantly higher than in culture only with TGF- or TGF- + ATRA. Same team also Guanabenz acetate IC50 demonstrated that ATRA inhibits only transcription, but not translation of IL-10 [5]. However, supplementation of diet with high dose of ATRA in Balb/c mice has significantly increased secretion of IL-10 in lymphocytes isolated from lymph nodes. However, these CD4+ cells were stimulated by influenza virus [6]. The discrepancy of results achieved in the cited works can be justified by a different approach taken to antigenic stimulation. As well as IL-10, IL-35 is also a suppressive cytokine known to have an inhibitory effect on lymphocyte proliferation and effector Th17 of CD4+ CD25+ cells [7, 8]. Kochetkov have proven the anti-inflammatory effect of IL-35 in CIA in DBA/1 Guanabenz acetate IC50 mice in the context of production of IL-10 by CD4+ CD39+ or CD4+ CD39C. Both C57BL/6 and IL-10 C/C mice were administered orally 0.75 mg IL-35 or PBS. Subsequently, CIA was induced in mice. Animals that received IL-35 did not have any characteristic clinical symptoms of CIA [9]. On the additional hand, the reduced suppressive activity of Treg cells, as well as their Guanabenz acetate IC50 reduced rate of recurrence investigated under conditions, is definitely characteristic for individuals with autoimmune diseases, including type 1 diabetes, multiple sclerosis [10], and rheumatoid arthritis [11]. The emergence of effective methods of development of polyclonal Treg lymphocytes offers made it possible to attempt cellular immunotherapy in animal model diseases and in humans affected by autoimmune diseases, as well as in transplantation medicine [12]. In animal models of autoimmune diseases it was found that adoptive transfer of Treg lymphocytes may efficiently lessen the progression of the disease. Morgan conditions reduces medical symptoms of CIA in Wistar rodents [16]. Among the many providers used for the induction of the differentiation of CD4+ lymphocytes into iTreg cells, rapamycin and all-trans-retinoic acid (ATRA) seem to become most effective. Under their influence the caused lymphocytes gain stable phenotype of Treg cells that are able to preserve its immunosuppressive function towards the effector lymphocytes. ATRA is definitely thought to regulate the foxp3 gene appearance by inducing chromatin decondensation and histone acetyltransferase recruitment in the promoter region. However, ATRA does not constantly increase foxp3 appearance in lymphocytes in the cytokine environment, which assures the differentiation towards Treg [17], but it exerts a positive influence on the induction of additional Treg cell features. Among others, it raises the appearance of chemokines, assuring.