From the Research
Role of FoxP3 in Kidney Injury and Acute Renal Failure
- FoxP3 is a master transcription factor in regulatory T cell (Treg) development and plays a protective role in glomerulonephritis (GN) and kidney injury 1.
- The protective role of FoxP3 in crescentic GN is associated with a markedly suppressed expression of proinflammatory cytokines, such as IL-1β, TNF-α, and MCP-1, and diminished infiltration of the kidneys by CD3+ T cells and F4/80+ macrophages 1.
- Overexpression of FoxP3 results in a significant increase in CD4+ Foxp3+ Tregs systemically and in the diseased kidneys, thereby blunting Th1, Th2, and Th17 responses systemically and in the kidneys 1.
Mechanisms of FoxP3 in Regulating Immune Responses
- FoxP3 relies heavily on high and stable expression to activate anti-inflammatory genes and repress proinflammatory genes, and is required to shape the unique signaling mechanisms in Tregs 2.
- FoxP3 achieves its function in concert with several other transcription factors, many of which are associated with lineages of conventional T cells, and enables Treg plasticity 2.
- FoxP3 serves as a highly connected 'hub', interacting with numerous genomic sites and partner proteins, in the molecular network that orchestrates multiple facets of Treg cell differentiation and function 3.
Modes of Immune Suppression by FoxP3+ Regulatory T Cells
- FoxP3+ regulatory T cells (Tregs) can suppress excessive or aberrant immune responses through two modes: deprivation of activation signals in physiological and steady states, and active damping of excessive immune responses in highly inflammatory environments 4.
- In inflammatory conditions, activated Tregs acquire the capacity to kill or inactivate effector T cells and antigen-presenting cells, thereby actively suppressing immune responses 4.
Role of FoxP3 in the Immune System
- FoxP3 is a member of the forkhead transcription factor family and is mainly expressed in a subset of CD4+ T-cells that play a suppressive role in the immune system 5.
- FoxP3 suppresses the function of NFAT and NFkappaB, leading to suppression of expression of many genes, including IL-2 and effector T-cell cytokines, and acts as a transcription activator for many genes, including CD25, CTLA4, and GITR 5.