Requirement of Treg-intrinsic CTLA4/PKCη signaling pathway for suppressing tumor immunity.

All-trans Retinoic Acid Regulates the Balance of Treg-Th17 Cells through ERK and P38 Signaling Pathway

Opposing effects of CTLA4 insufficiency on regulatory versus conventional T cells in autoimmunity converge on effector memory in target tissue.

Quantitative variations in CTLA4 expression, because of genetic polymorphisms, are associated with various human autoimmune conditions, including type 1 diabetes (T1D). Extensive studies have demonstrated that CTLA4 is not only essential for the suppressive role of regulatory T cells (T(reg)) but also required for intrinsic control of conventional T (T(conv)) cells. We report that a modest insu...

Extrinsic MAVS signaling is critical for Treg maintenance of Foxp3 expression following acute flavivirus infection

Given the rapid spread of flaviviruses such as West Nile virus (WNV) and Zika virus, it is critical that we develop a complete understanding of the key mediators of an effective anti-viral response. We previously demonstrated that WNV infection of mice deficient in mitochondrial antiviral-signaling protein (MAVS), the signaling adaptor for RNA helicases such as RIG-I, resulted in increased deat...

CTLA4 expression is an indicator and regulator of steady-state CD4+ FoxP3+ T cell homeostasis.

The presence of FoxP3(+) regulatory T cells (Tregs) is necessary for control of deleterious immune responses in the steady state; however, mechanisms for maintaining the frequency and quality of endogenous Tregs are not well defined. In this study, we used in vivo modulators of the CD28 and CTLA4 pathways administered to intact mice to reveal mechanisms controlling the homeostasis and phenotype...

Attenuation of CD4+ CD25+ Regulatory T Cells in the Tumor Microenvironment by Metformin, a Type 2 Diabetes Drug

CD4+CD25+ regulatory T cells (Treg), an essential subset for preventing autoimmune diseases, is implicated as a negative regulator in anti-tumor immunity. We found that metformin (Met) reduced tumor-infiltrating Treg (Ti-Treg), particularly the terminally-differentiated CD103+KLRG1+ population, and also decreased effector molecules such as CTLA4 and IL-10. Met inhibits the differentiation of na...