Tregs in Autoimmunity: Insights Into Intrinsic Brake Mechanism Driving Pathogenesis and Immune Homeostasis

Abstract

CD4+CD25highFoxp3+ regulatory T-cells (Tregs) are functionally characterized for their ability to suppress the activation of multiple immune cell types and are indispensable for maintaining immune homeostasis and tolerance. Disruption of this intrinsic brake system assessed by loss of suppressive capacity, cell numbers, and Foxp3 expression, leads to uncontrolled immune responses and tissue damage. The conversion of Tregs to a pathogenic pro-inflammatory phenotype is widely observed in immune mediated diseases. However, the molecular mechanisms that underpin the control of Treg stability and suppressive capacity are incompletely understood. This review summarizes the concepts of Treg cell stability and Treg cell plasticity highlighting underlying mechanisms including translational and epigenetic regulators that may enable translation to new therapeutic strategies. Our enhanced understanding of molecular mechanism controlling Tregs will have important implications into immune homeostasis and therapeutic potential for the treatment of immune-mediated diseases.

Identification of MYEOV-Associated Gene Network as a Potential Therapeutic Target in Pancreatic Cancer

“…In contrast, CD4 T cells, γδT cells, MAIT cells, NK cells, Tfh cells, and CD8T cells were downregulated immune cells in pancreatic cancer ( Figure 6 B,C). This suggests that EGFR, SERPINB5, MYEOV, GPRC5A, and KRAS may drive further pancreatic cancer development by recruiting pro-tumor-associated immune cells such as monocytes, nTreg cells, and Th17 cells through downstream responses while inhibiting the infiltration of tumor-suppressive immune cells such as CD4 T cells, γδT cells, MAIT cells, NK cells, Tfh cells, and CD8T cells to reduce tumor-associated immune killing [ 19 , 20 , 21 , 22 ]. All these results further corroborate and explain our speculation about the role of the molecular network of MYEOV-related genes for pancreatic cancer.…”

Glutaminolysis of CD4+ T Cells: A Potential Therapeutic Target in Viral Diseases

“…Regulatory T (Treg) cells, a subset of helper T cells, are pivotal in supporting immune tolerance and preventing autoimmunity. 23 , 24 Forkhead box protein P3 (Foxp3) is a master transcription factor for Tregs. Conventional CD4 + T cells activated during immune responses may acquire Foxp3 expression under adequate conditions and become peripherally induced Treg (pTreg) cells, which can be further differentiated into peripherally induced Tregs (iTregs), IL-10-producing Tregs and TGF-β-producing Th3 cells 25 , 26 ( Figure 2 ).…”

Oncogenesis and autoimmunity as a result of mRNA COVID-19 vaccination

“…This can be expected to cause excessive immune suppression in the tumor microenvironment, leading to accelerated tumor progression. Autoimmune disease has the opposite problem [45,75]. The increased activation of Teff cells by the vaccine in the context of an insufficient Treg pool will exacerbate autoimmune disease.…”