title: Human mast cells drive memory CD4+ T cells toward an inflammatory IL-22+ phenotype.
abstract: BACKGROUND
  Mast cells are key components of the skin microenvironment in psoriasis, yet their functional role in this T-cell-mediated inflammatory disorder remains to be elucidated.
  
  
  OBJECTIVE
  To define the impact of T-cell/mast-cell cognate interactions on the cytokines produced by TH cells.
  
  
  METHODS
  We used human primary mast cells and effector/memory CD4(+) T cells for in vitro coculture experiments, and we analyzed TH cells responses by using cytometry. CD4(+) T-cell/mast-cell conjugates in skin lesions from patients with psoriasis were analyzed by using 3-color immunohistochemistry and confocal microscopy.
  
  
  RESULTS
  We show that IFN-γ-primed human mast cells formed productive immunologic synapses with antigen-experienced CD4(+) T cells. These interactions promoted the generation of TH22 and IL-22/IFN-γ-producing TH cells from the circulating memory CD4(+) T-cell pool via a TNF-α/IL-6-dependent mechanism. An analysis of human psoriatic skin biopsies showed a rich infiltrate of IL-22(+)CD4(+) T cells frequently found in contact with mast cells. Moreover, most of these mast-cell-conjugated lymphocytes coexpressed IFN-γ, suggesting that IL-22(+)IFN-γ(+) CD4(+) T cells are generated in vivo on interaction with mast cells.
  
  
  CONCLUSIONS
  Our findings identify human mast cells as functional partners of TH cells, shaping their responses toward IL-22 production.
authors.affiliation: Institut National de la Santé et de la Recherche Médicale, Université de Toulouse, Toulouse, France.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Gaudenzio
authors.forename: Camille
authors.initials: C
authors.lastname: Laurent
authors.forename: Salvatore
authors.initials: S
authors.lastname: Valitutti
authors.forename: Eric
authors.initials: E
authors.lastname: Espinosa
mesh_terms: D015496:CD4-Positive T-Lymphocytes / Q000145:classification / Q000276:immunology* / Q000473:pathology; D002450:Cell Communication / Q000235:genetics / Q000276:immunology; D018920:Coculture Techniques; D006801:Humans; D007156:Immunologic Memory / Q000235:genetics; D016130:Immunophenotyping; D018836:Inflammation Mediators / Q000378:metabolism / Q000502:physiology*; D007378:Interleukins / Q000096:biosynthesis* / Q000235:genetics; D008407:Mast Cells / Q000276:immunology* / Q000473:pathology; D000097043:Interleukin-22
chemical_list: D018836:Inflammation Mediators; D007378:Interleukins; D000097043:Interleukin-22