title: Human mast cells are major IL-22 producers in patients with psoriasis and atopic dermatitis.
abstract: BACKGROUND
  Psoriasis is a systemic inflammatory disease in which IL-17 and IL-22 levels are markedly increased in the skin and blood. The prevalent concept, using skin cells that are isolated from psoriatic plaques and examined after cell expansion and in vitro stimulation, is that IL-17 and IL-22 production essentially results from T cells and the rare type 3 innate lymphoid cells.
  
  
  OBJECTIVE
  We sought to examine the cellular source of IL-17A and IL-22 at the protein and transcriptional single-cell level immediately after ex vivo skin cell isolation from psoriatic plaques.
  
  
  METHODS
  Skin biopsy specimens were collected from patients with psoriasis, as well as from patients with atopic dermatitis. Cell suspensions were prepared by combining mild enzymatic digestion and mechanical dissociation and analyzed for cytokine expression without prior in vitro culture and stimulation. Expression of IL-17 and IL-22 was quantified at the protein and mRNA single-cell level by using flow cytometry.
  
  
  RESULTS
  IL-22 is predominantly expressed by CD3(-)c-Kit(+) cells relative to CD3(+) T cells in lesional skin of patients with psoriasis and patients with atopic dermatitis. Strikingly, we identified c-Kit(+)FcεRI(+) mast cells as major IL-22 producers. The proportion of mast cells that produce IL-22 ranges from 20% to 80% in patients with psoriasis or those with atopic dermatitis. Skin mast cells express IL-22 and IL-17 mRNA. Conversely, IL-17-producing T cells outnumber IL-17-producing mast cells, which also express IL-17 receptor.
  
  
  CONCLUSIONS
  Human skin mast cells are previously unrecognized IL-22 producers. We further established that skin mast cells express IL-17. Thus mast cells might play an important role in the physiopathology of chronic inflammatory skin disorders.
authors: Immunoregulation Laboratory, Centre de Recherche du Centre Hospitalier de l'Université de Montréal (CRCHUM), Montreal, Quebec, Canada.
authors: Shunya
authors: S
authors: Mashiko
authors: Immunoregulation Laboratory, Centre de Recherche du Centre Hospitalier de l'Université de Montréal (CRCHUM), Montreal, Quebec, Canada.
authors: Salim
authors: S
authors: Bouguermouh
authors: Immunoregulation Laboratory, Centre de Recherche du Centre Hospitalier de l'Université de Montréal (CRCHUM), Montreal, Quebec, Canada.
authors: Manuel
authors: M
authors: Rubio
authors: Center for Innovative and Translational Medicine, Kochi University Medical School, Nankoku, Kochi, Japan.
authors: Nobuyasu
authors: N
authors: Baba
authors: Innovaderm Research, Montreal, Quebec, Canada.
authors: Robert
authors: R
authors: Bissonnette
authors: Immunoregulation Laboratory, Centre de Recherche du Centre Hospitalier de l'Université de Montréal (CRCHUM), Montreal, Quebec, Canada. Electronic address: m.sarfati@umontreal.ca.
authors: Marika
authors: M
authors: Sarfati
mesh_terms: D017252:CD3 Complex / Q000235:genetics / Q000276:immunology; D002452:Cell Count; D003876:Dermatitis, Atopic / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D015870:Gene Expression; D006801:Humans; D020381:Interleukin-17 / Q000235:genetics / Q000276:immunology*; D007378:Interleukins / Q000235:genetics / Q000276:immunology*; D008407:Mast Cells / Q000276:immunology* / Q000473:pathology; D061251:Primary Cell Culture; D019009:Proto-Oncogene Proteins c-kit / Q000235:genetics / Q000276:immunology; D011565:Psoriasis / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D012333:RNA, Messenger / Q000235:genetics / Q000276:immunology; D017455:Receptors, IgE / Q000235:genetics / Q000276:immunology; D053722:Receptors, Interleukin-17 / Q000235:genetics / Q000276:immunology; D012867:Skin / Q000276:immunology / Q000473:pathology; D013601:T-Lymphocytes / Q000276:immunology* / Q000473:pathology; D000097043:Interleukin-22
chemical_list: D017252:CD3 Complex; D020381:Interleukin-17; D007378:Interleukins; D019009:Proto-Oncogene Proteins c-kit; D012333:RNA, Messenger; D017455:Receptors, IgE; D053722:Receptors, Interleukin-17; D000097043:Interleukin-22; C508717:IL17A protein, human
keywords: IL-17; IL-22; Mast cells; T cells; atopic dermatitis; psoriasis