title: Forkhead Box P family members at the crossroad between tolerance and immunity: a balancing act.
abstract: Maintaining an immune balance between a chronic inflammatory state and autoimmunity is regulated at multiple levels by complex cellular signaling mechanisms. Numerous immune stimulatory and inhibitory signals converge on a large variety of transcriptional regulators. One key transcriptional regulator of immune homeostasis is FOXP3, which is a member of the Forkhead Box P subfamily of transcription factors and was shown to be essential for the development and maintenance of regulatory T cells. However, other FOXP members have received less attention in relation to a role in immune regulation. Still, recent developments point toward a general important regulatory role for FOXP proteins in the development and function of the adaptive immune system and establishment of a balanced immune response. Here, we discuss the current knowledge on the role of FOXP proteins in establishing immune homeostasis with an emphasis on T-cell biology. Furthermore, we review and speculate about different modes of regulating general FOXP activity and the function of this in health and disease.
authors.affiliation: Department of Cell Biology, University Medical Center Utrecht , Utrecht , The Netherlands.
authors.forename: Veerle
authors.initials: V
authors.lastname: Fleskens
authors.forename: Ruben
authors.initials: R
authors.lastname: van Boxtel
mesh_terms: D056704:Adaptive Immunity; D000818:Animals; D015551:Autoimmunity; D051858:Forkhead Transcription Factors / Q000276:immunology* / Q000378:metabolism; D005786:Gene Expression Regulation / Q000276:immunology; D006706:Homeostasis; D006801:Humans; D007108:Immune Tolerance; D015398:Signal Transduction; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*
chemical_list: C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors