In human disease, alterations in numbers of regulatory T cells – and in particular those that express<unk>  – are found in a number of disease states. For example, patients with tumors have a local relative excess of<unk>  positive T cells which inhibits the body's ability to suppress the formation of cancerous cells. Conversely, patients with an autoimmune disease such as systemic lupus erythematosus (SLE) have a relative dysfunction of<unk>  positive cells. The<unk>  gene is also mutated in IPEX syndrome (Immunodysregulation, Polyendocrinopathy, and Enteropathy, X-linked). Many patients with IPEX have mutations in the DNA-binding forkhead domain of<unk> . In mice, a<unk>  mutation (a frameshift mutation that result in protein lacking the forkhead domain) is responsible for 'Scurfy', an X-linked recessive mouse mutant that results in lethality in hemizygous males 16 to 25 days after birth. These mice have overproliferation of CD4+ T-lymphocytes, extensive multiorgan infiltration, and elevation of numerous cytokines. This phenotype is similar to those that lack expression of CTLA-4, TGF-β, human disease IPEX, or deletion of the<unk>  gene in mice ("scurfy mice"). The pathology observed in scurfy mice seems to result from an inability to properly regulate CD4+ T-cell activity. In mice overexpressing the<unk>  gene, fewer T cells are observed. The remaining T cells have poor proliferative and cytolytic responses and poor interleukin-2 production, although thymic development appears normal. Histologic analysis indicates that peripheral lymphoid organs, particularly lymph nodes, lack the proper number of cells.
FOXP3
FOXC2
FOXF1
Mad2
SOX2
CDK13
INK4
TFM-4AS-1