Abstract
Regulatory T (Treg) cells are essential for normal immune surveillance systems, and their dysfunction leads to development of diseases, such as autoimmune disorders. CD4+CD25+ Treg cells are well-known suppressive cells, which express the transcription factor Foxp3, are indispensable for the maintenance of immune self-tolerance and homeostasis by suppressing aberrant or excessive immune response. Other Foxp3− Treg cells include Tr1, Th3, CD8+CD28−/−, and Qa1-restricted T cells; however, the contribution of these Treg cells to self-tolerance, immune homeostasis as well as preventing autoimmunity is not well defined. Here, we discuss the phenotypes and function of Foxp3+ Treg cells and the potential use of such Treg cells against rheumatoid arthritis (RA). Of note, even though most expanded populations of Foxp3+ Treg cells exhibit suppressive activity, tissue-associated or antigen-specific Treg cells appear superior in suppressing local autoimmune disorders such as RA. In addition, utilizing tissue-associated Foxp3+ Treg cells from stem cells may stable Foxp3 expression and avoid induction of a potentially detrimental systemic immunosuppression.
Highlights
Rheumatoid arthritis (RA) is a chronic autoimmune disorder, which has approximately 1% prevalence in the industrialized world, and is described by pain and stiffness of the joints, and inflammation of the synovial membrane
Regulatory T cells in autoimmunity of studies have addressed that the majority of the forkhead box P3 (Foxp3)+ Treg cells are produced in the thymus as an antigen-primed and functionally mature T cell subpopulation specialized for immune suppression
Several questions remain: (i) how to direct the differentiation of Treg cells, (ii) how to obtain a large number of functional Treg cells, and (iii) which type of stem cells can be feasibly applicable for individual use
Summary
Regulatory T (Treg) cells are essential for normal immune surveillance systems, and their dysfunction leads to development of diseases, such as autoimmune disorders. CD4+CD25+ Treg cells are well-known suppressive cells, which express the transcription factor Foxp, are indispensable for the maintenance of immune self-tolerance and homeostasis by suppressing aberrant or excessive immune response. Other Foxp3− Treg cells include Tr1, Th3, CD8+CD28−/−, and Qa1-restricted T cells; the contribution of these Treg cells to self-tolerance, immune homeostasis as well as preventing autoimmunity is not well defined. Even though most expanded populations of Foxp3+ Treg cells exhibit suppressive activity, tissue-associated or antigen-specificTreg cells appear superior in suppressing local autoimmune disorders such as RA. Utilizing tissue-associated Foxp3+ Treg cells from stem cells may stable Foxp expression and avoid induction of a potentially detrimental systemic immunosuppression
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