title: Inhibition of differentiation, amplification, and function of human TH17 cells by intravenous immunoglobulin.
abstract: BACKGROUND
  T(H)17 cells play a critical role in the pathogenesis of several autoimmune and allergic diseases. Intravenous immunoglobulin (IVIg), a therapeutic preparation of polyclonal IgG that is increasingly used in the treatment of diverse autoimmune and allergic diseases, might target T(H)17 cells to exert therapeutic effects.
  
  
  OBJECTIVE
  We sought to examine whether IVIg interferes with the development and function of human T(H)17 cells.
  
  
  METHODS
  T(H)17 cells were differentiated from naive human CD4(+) T cells in the presence of TGF-β and IL-21. T(H)17 cells were amplified by stimulating memory CD4(+) T cells in the presence of IL-1β and IL-6. The effect of IVIg was examined on the differentiation and amplification of T(H)17 cells, expression of the T(H)17 lineage-specific transcription factor retinoic acid-related orphan receptor C, secretion of T(H)17 effector cytokines, and phosphorylation of signal transducer and activator of transcription 3, a transcription factor that plays an important role in T(H)17 cell development and function.
  
  
  RESULTS
  IVIg inhibits the differentiation and amplification of human T(H)17 cells, as well as the production of their effector cytokines IL-17A, IL-17F, IL-21, and CCL20. The inhibitory effects of IVIg on T(H)17 cells are F(ab')(2) dependent and involve interference with the expression of retinoic acid-related orphan receptor C and activation of signal transducer and activator of transcription 3. Also, IVIg significantly enhanced forkhead box protein 3-positive regulatory T cells among the memory CD4(+) T cells.
  
  
  CONCLUSIONS
  These results reveal a novel mechanism of action of IVIg in achieving a therapeutic effect in autoimmune and allergic diseases, in which T(H)17 cells play a key modulatory role in sustaining the chronic inflammatory response. Our results also suggest a reciprocal regulation of T(H)17 and regulatory T-cell populations by IVIg.
authors.affiliation: Unité 872, Institut National de la Santé et de la Recherche Médicale Paris, Paris, France.
authors.forename: Mohan S
authors.initials: MS
authors.lastname: Maddur
authors.forename: Janakiraman
authors.initials: J
authors.lastname: Vani
authors.forename: Pushpa
authors.initials: P
authors.lastname: Hegde
authors.forename: Sebastien
authors.initials: S
authors.lastname: Lacroix-Desmazes
authors.forename: Srini V
authors.initials: SV
authors.lastname: Kaveri
authors.forename: Jagadeesh
authors.initials: J
authors.lastname: Bayry
mesh_terms: D002454:Cell Differentiation / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects; D016207:Cytokines / Q000037:antagonists & inhibitors / Q000378:metabolism; D006801:Humans; D016756:Immunoglobulins, Intravenous / Q000276:immunology / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects; D058504:Th17 Cells / Q000187:drug effects* / Q000276:immunology*
chemical_list: D016207:Cytokines; D016756:Immunoglobulins, Intravenous