title: Origin and functions of pro-inflammatory cytokine producing Foxp3+ regulatory T cells.
abstract: CD4(+)CD25(+)Foxp3(+) regulatory cells (Tregs) are a special lineage of cells central in the maintenance of immune homeostasis, and are targeted for human immunotherapy. They are conventionally associated with the production of classical anti-inflammatory cytokines such as IL-10, TGF-β and IL-35, consistent to their anti-inflammatory functions. However, emerging evidence show that they also express effector cytokines such as IFN-γ and IL-17A under inflammatory conditions. While some studies reveal that these pro-inflammatory cytokine producing Foxp3(+) regulatory cells retain their suppressive ability, others believe that these cells are dys-regulated and are associated with perpetuation of immunopathology. Therefore the development of these cells may challenge the efficacy of human Treg therapy. Mechanistically, toll-like receptor (TLR) ligands and the pro-inflammatory cytokine milieu have been shown to play important roles in the induction of effector cytokines in Tregs. Here we review the mechanisms of development and the possible functions of pro-inflammatory cytokine producing Foxp3+ Tregs.
authors.affiliation: Department of Biological Sciences, School of Dental Medicine, Case Western Reserve University, Cleveland, OH 44106, USA. Electronic address: pxp226@case.edu.
authors.forename: Pushpa
authors.initials: P
authors.lastname: Pandiyan
authors.affiliation: Molecular and Cellular Immunoregulation Unit, Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
authors.forename: Jinfang
authors.initials: J
authors.lastname: Zhu
mesh_terms: D016207:Cytokines / Q000096:biosynthesis / Q000276:immunology*; D051858:Forkhead Transcription Factors / Q000032:analysis; D006801:Humans; D007111:Immunity, Cellular / Q000276:immunology; D007371:Interferon-gamma / Q000276:immunology; D016753:Interleukin-10 / Q000276:immunology; D020381:Interleukin-17 / Q000096:biosynthesis / Q000276:immunology; D007378:Interleukins / Q000096:biosynthesis / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000473:pathology; D058504:Th17 Cells / Q000276:immunology
chemical_list: D016207:Cytokines; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; C508609:IL10 protein, human; C508717:IL17A protein, human; D020381:Interleukin-17; D007378:Interleukins; C532417:interleukin-35, human; D016753:Interleukin-10; D007371:Interferon-gamma
keywords: Cytokine; Foxp3; IL-17; Inflammation; Reprogramming; Suppression; T(reg); Th17