title: Modulation of IL-17 and Foxp3 expression in the prevention of autoimmune arthritis in mice.
abstract: BACKGROUND
  Rheumatoid Arthritis (RA) is a chronic immune mediated disease associated with deregulation of many cell types. It has been reported that different T cell subsets have opposite effects in disease pathogenesis, in particular Th17 and Treg cells.
  
  
  RESULTS
  We investigated whether non-depleting anti-CD4 monoclonal antibodies, which have been reported as pro-tolerogenic, can lead to protection from chronic autoimmune arthritis in SKG mice--a recently described animal model of RA--by influencing the Th17/Treg balance. We found that non-depleting anti-CD4 prevented the onset of chronic autoimmune arthritis in SKG mice. Moreover, treated mice were protected from the induction of arthritis up to 60 days following anti-CD4 treatment, while remaining able to mount CD4-dependent immune responses to unrelated antigens. The antibody treatment also prevented disease progression in arthritic mice, although without leading to remission. Protection from arthritis was associated with an increased ratio of Foxp3, and decreased IL-17 producing T cells in the synovia. In vitro assays under Th17-polarizing conditions showed CD4-blockade prevents Th17 polarization, while favoring Foxp3 induction.
  
  
  CONCLUSIONS
  Non-depleting anti-CD4 can therefore induce long-term protection from chronic autoimmune arthritis in SKG mice through reciprocal changes in the frequency of Treg and Th17 cells in peripheral tissues, thus shifting the balance towards immune tolerance.
authors.affiliation: Instituto de Medicina Molecular, Faculdade de Medicina, University of Lisbon, Lisbon, Portugal.
authors.forename: Joana
authors.initials: J
authors.lastname: Duarte
authors.forename: Ana
authors.initials: A
authors.lastname: Agua-Doce
authors.forename: Vanessa G
authors.initials: VG
authors.lastname: Oliveira
authors.forename: João Eurico
authors.initials: JE
authors.lastname: Fonseca
authors.forename: Luis
authors.initials: L
authors.lastname: Graca
mesh_terms: D000818:Animals; D000906:Antibodies / Q000627:therapeutic use; D001168:Arthritis / Q000188:drug therapy / Q000276:immunology* / Q000517:prevention & control*; D015551:Autoimmunity / Q000276:immunology*; D015704:CD4 Antigens / Q000276:immunology; D016764:Cell Polarity; D002908:Chronic Disease; D018450:Disease Progression; D051858:Forkhead Transcription Factors / Q000235:genetics / Q000378:metabolism*; D005786:Gene Expression Regulation; D007114:Immunization; D007121:Immunocompetence / Q000276:immunology; D020381:Interleukin-17 / Q000235:genetics / Q000378:metabolism*; D008198:Lymph Nodes / Q000276:immunology / Q000473:pathology; D051379:Mice; D013583:Synovial Membrane / Q000276:immunology / Q000473:pathology; D050378:T-Lymphocytes, Regulatory / Q000166:cytology / Q000276:immunology; D013997:Time Factors; D047071:beta-Glucans
chemical_list: D000906:Antibodies; D015704:CD4 Antigens; D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; D020381:Interleukin-17; D047071:beta-Glucans; C038459:curdlan