The Role of MicroRNAs in Regulatory T Cells and in the Immune Response

The discovery of microRNA (miRNA) is one of the major scientific breakthroughs in recent years and has revolutionized current cell biology and medical science. miRNAs are small (19~25nt) noncoding RNA molecules that post-transcriptionally regulate gene expression by targeting the 3' untranslated region (3'UTR) of specific messenger RNAs (mRNAs) for degradation of translation repression. Genetic ablation of the miRNA machinery, as well as loss or degradation of certain individual miRNAs, severely compromises immune development and response, and can lead to immune disorders. Several sophisticated regulatory mechanisms are used to maintain immune homeostasis. Regulatory T (Treg) cells are essential for maintaining peripheral tolerance, preventing autoimmune diseases and limiting chronic inflammatory diseases. Recent publications have provided compelling evidence that miRNAs are highly expressed in Treg cells, that the expression of Foxp3 is controlled by miRNAs and that a range of miRNAs are involved in the regulation of immunity. A large number of studies have reported links between alterations of miRNA homeostasis and pathological conditions such as cancer, cardiovascular disease and diabetes, as well as psychiatric and neurological diseases. Although it is still unclear how miRNA controls Treg cell development and function, recent studies certainly indicate that this topic will be the subject of further research. The specific circulating miRNA species may also be useful for the diagnosis, classification, prognosis of diseases and prediction of the therapeutic response. An explosive literature has focussed on the role of miRNA. In this review, I briefly summarize the current studies about the role of miRNAs in Treg cells and in the regulation of the innate and adaptive immune response. I also review the explosive current studies about clinical application of miRNA.

The Role of Regulatory T Cells in Cancer

There has been an explosion of literature focusing on the role of regulatory T (Treg) cells in cancer immunity. It is becoming increasingly clear that Treg cells play an active and significant role in the progression of cancer, and have an important role in suppressing tumor-specific immunity. Thus, there is a clear rationale for developing clinical strategies to diminish their regulatory influences, with the ultimate goal of augmenting antitimor immunity. Therefore, manipulation of Treg cells represent new strategies for cancer treatment. In this Review, I will summarize and review the explosive recent studies demonstrating that Treg cells are increased in patients with malignancies and restoration of antitumor immunity in mice and humans by depletion or reduction of Treg cells. In addition, I will discuss both the prognostic value of Treg cells in tumor progression in tumor-bearing hosts and the rationale for strategies for therapeutic vaccination and immunotherapeutic targeting of Treg cells with drugs and microRNA.

Regulatory T Cell Therapy for Autoimmune Disease

It has now been well documented in a variety of models that T regulatory T cells (Treg cells) play a pivotal role in the maintenance of self-tolerance, T cell homeostasis, tumor, allergy, autoimmunity, allograft transplantation and control of microbial infection. Recently, Treg cell are isolated and can be expanded in vitro and in vivo, and their role is the subject of intensive investigation, particularly on the possible Treg cell therapy for various immune-mediated diseases. A growing body of evidence has demonstrated that Treg cells can prevent or even cure a wide range of diseases, including tumor, allergic and autoimmune diseases, transplant rejection, graft-versus-host disease. Currently, a large body of data in the literature has been emerging and provided evidence that clear understanding of Treg cell work will present definite opportunities for successful Treg cell immunotherapy for the treatment of a broad spectrum of diseases. In this Review, I briefly discuss the biology of Treg cells, and summarize efforts to exploit Treg cell therapy for autoimmune diseases. This article also explores recent observations on pharmaceutical agents that abrogate or enhance the function of Treg cells for manipulation of Treg cells for therapeutic purpose.

The Role of Suppressor T Cells in Mycobacterial Infection / 나학회지

Suppressor T cells (Ts cells) once became probably the most controversial topic in the field of immunology. However, recently the picture has changed dramatically. Suppressor T cells, now less provocatively renamed regulatory T cells (Treg cells) are isolated and can be expanded in vitro and in vivo and their role is the subject of intensive investigation. It is now well recognized that Treg cell is central components of fundamental immune functions such as self-tolerance, anti-tumor response, T cell homeostasis, allergic and autoimmune diseases, allograft transplantation and control of infection. Although regulatory T cells play a crucial role in the control of immune responses to bacteria, fungus, virus and parasites, little is known about the role of Treg cells in mycobacterial infections. Here, I briefly describe 1)the biology of Treg cells, 2)induction and expansion of pathogen-specific Treg cells, 3)beneficial and detrimental roles of Treg cells in infection and 4)"Old Friends" mechanism of hygiene hypothesis. This article also explores observations on Treg or Ts cells in mycobacterial infectious diseases such as leprosy and tuberculosis. I finally summarize the potential for Treg-targeted immunotherapy in infectious diseases allergic and autoimmune diseases as well as transplantation and anti-tumor immunity. The correct balance of effector/pathogenic and regulatory T cells for successful immunotherapeutic approach is also emphasized.

Effects of thymosin and insulin on suppressor T cell in type Ⅱdiabetes / 中国糖尿病杂志

The activity and the percentage of suppressor T cells in PBMC from 28 patients with type I diabetes of various durations treated with thymosin or insulin were detected by using the method of ConA-induced suppressor T cells and Wu T8 (suppressor/cytotoxic) monoclonal antibody respectively. Both thymosin and insulin were found to have ability to improve and normalize the ConA-induced suppressor cell activity and the percentage of Wu T8 cells in diabetic patients. The maximal effects were found at the concentration of 3. 22?mol/L thymosin and 1. 722nmol/L(240. 05mIU /L) insulin. Thymosin was more effective than insulin.