Description

Regulatory T cells (Tregs) play a fundamental role in maintaining immune homeostasis by modulating the immune response against self-antigens, allergens, pathogens as well as tumors. While Tregs were originally thought to be a terminally-differentiated population of T cells whose only function was to inhibit the activation and/or proliferation of immune cells, studies over the past decade have established that Tregs have a far broader role mediated by their interaction with several immune and non-immune cells. For instance, Tregs interact with monocytes and NK cells modulating their phenotype and/or functions towards a more anti-inflammatory state. Tregs can also interact with non-immune cells. For example, they accumulate in skeletal muscle after injury and mediate tissue repair functions. Under inflammatory conditions, Tregs can produce pro-inflammatory cytokines such as IFNγ and acquire an aberrant effector-like phenotype (plasticity) or even lose Foxp3 expression (instability) in disease settings such as autoimmune, allergic and infectious diseases. An example of these events occurs in patients with relapsing-remitting Multiple Sclerosis (MS), who display an increased frequency of IFNγ-producing Th1-like Tregs and a decrease in Treg suppressive function. Furthermore, a small percentage of Tregs in mouse models of MS have been shown to lose Foxp3 expression and become effector T cells, producing pro-inflammatory cytokines (IFNγ and IL-17) and contributing to disease severity.

While these Treg plasticity and instability events are controlled by intrinsic molecular signaling pathways such as the PI3K/AKT pathway, the activation of such pathways that modify Treg phenotype and function is modulated by their environment. In this regard, it has been shown that pro-inflammatory cytokines, some dietary factors, and even acute infections can induce Treg plasticity and instability.

Altogether, these observations have opened a new field of investigation focused on understanding the immunological mechanisms underlying these events, their biological significance and the role of the environment in their modulation. This novel information on control of Treg stability, plasticity and function could lead to the development of therapies to treat cancer or autoimmunity.

In this Research Topic, we welcome the submission of Reviews, Mini-reviews and Original Research Articles that provide an update on the research being performed to dissect (i) the molecular mechanisms underlying Treg function, plasticity and instability, and (ii) the influence of environmental factors on these mechanisms in health and disease. The topics that this article collection will cover include, but are not limited to, the following:

• Treg function, stability and plasticity in autoimmune, infectious, allergic diseases and cancer.
• Basic mechanisms of regulation of Foxp3 expression in Tregs during disease.
• Molecular and metabolic mechanisms that regulate Treg function, stability and plasticity.
• Environmental factors that modulate Treg stability, plasticity and/or function.