Regulatórikus T-sejtek glukokortikoid hormon érzékenységének modell vizsgálata és eltérései szisztémás szklerózisban

Abstract

Regulatory T cells (Treg) are a specialized subpopulation of T cells that play a key role in maintaining tolerance to self-antigens and in suppression of excessive immune response after antigenic stimulation, thereby helping to keep immune homeostasis and lower the risk for developing autoimmune diseases and allergies. Some of the clinically important issues are their participation in prevention of organ rejection after transplantation and tolerance to a fetus by the mother. The thus far best described subsets of Treg cells are the naturally arising thymus-derived (tTreg) Treg cells and the induced Treg (iTreg) cells that arise in the periphery recently also called peripheral Treg cells (pTreg). Both tTregs and pTregs express the characteristic transcription factor Foxp3 (Forkhead box protein 3), CD25, and CD4. Foxp3 is a member of the forkhead transcription factor family, which is defined by a common DNA-binding domain, termed the forkhead box or winged helix domain. The expression of Foxp3 is sufficient to generate T cells with a suppressive phenotype. Lineage specification factors play an important role in cellular differentiation by modulating expression of a broad set of genes whose expression patterns define functional and phenotypic properties of a given cell type. Foxp3 represents a rare example of a lineage specification factor with a specialized role in supporting differentiation and function of a single cell type, namely the Treg cells. Therefore, Foxp3 is considered a “master regulator” of Tregs. There are, however, emerging data suggesting that Foxp3 expression per se may not be sufficient for stable maintenance of Treg suppressive function or reliably defining functional Tregs. For example, activated effector T cells (Teff) can also transiently express Foxp3 without acquiring Treg suppressive activity and even produce proinflammatory cytokines upon activation. As a transcription factor, Foxp3 interacts with multiple transcription factors known to be involved in activation, differentiation, and response of CD4+ T cells to T cell antigen receptor (TCR) stimulation. On the other hand, Foxp3 may also act as a transcriptional co-repressor because it inhibits the activity of NFκB, CREB, and RORα. Thus, Foxp3 functions as a transcription activator and repressor by interacting with other transcription factors, and programs T cells in a direction to promote immune tolerance. For example, Foxp3 transcriptionally represses IL-2 and maintains suppressor functions of Tregs by interacting with a transcription factor, NFAT. Reciprocally, some transcription factor partners of Foxp3 facilitate the gene expression of Foxp3.