title: IL-22, but not IL-17, dominant environment in cutaneous T-cell lymphoma.
abstract: OBJECTIVE
  Both patients with cutaneous T-cell lymphoma (CTCL) and those with atopic dermatitis (AD) have pruritus, T(H)2-biased T cells, and a tendency to have bacterial infections, suggesting a common pathologic basis for these two diseases. Recently, interleukin (IL)-22-producing T cells were reported in skin of patients with AD. In this study, we investigated expression levels of T(H)22- and T(H)17-related molecules in lesional skin and sera isolated from patients with CTCL.
  
  
  METHODS
  Skin biopsies and sera were collected from patients with CTCL or psoriasis and from healthy volunteers. Protein and mRNA expression levels of IL-22, IL-17A, IL-17F, IL-23p19, IL-10, IL-4, CCL20, CCR6, IL-8, and IL-20 were examined in lesional tissue and a subset of these molecules in sera. Phosphorylation of STAT3 was also assessed in lesional skin of CTCL and psoriasis by immunohistochemistry.
  
  
  RESULTS
  IL-22, IL-10, IL-4, CCL20, and CCR6 mRNA and protein levels, but not IL-17A, IL-17F, IL-23p19, IL-8, or IL-20, were significantly elevated in lesional skin of CTCL. Phosphorylation of STAT3 was detected in epidermis of CTCL skin. Moreover, serum IL-22, IL-10, and CCL20 levels were increased in CTCL and correlated with disease severity.
  
  
  CONCLUSIONS
  Our results suggest that IL-22 is important in establishing the tumor microenvironment for CTCL. Enhanced expression of CCL20 may explain epidermal hyperplasia and migration of CCR6(+) cells, such as Langerhans cells, into lesional skin. Relatively low expression of IL-17 may explain the lack of neutrophils in lesions of CTCL, which correlates with bacterial infections that commonly occur in skin affected by CTCL.
authors: Department of Dermatology, Faculty of Medicine, University of Tokyo, Tokyo, Japan.
authors: Tomomitsu
authors: T
authors: Miyagaki
authors: Makoto
authors: M
authors: Sugaya
authors: Hiraku
authors: H
authors: Suga
authors: Masahiro
authors: M
authors: Kamata
authors: Hanako
authors: H
authors: Ohmatsu
authors: Hideki
authors: H
authors: Fujita
authors: Yoshihide
authors: Y
authors: Asano
authors: Yayoi
authors: Y
authors: Tada
authors: Takafumi
authors: T
authors: Kadono
authors: Shinichi
authors: S
authors: Sato
mesh_terms: D000328:Adult; D054418:Chemokine CCL20 / Q000097:blood / Q000235:genetics* / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D016753:Interleukin-10 / Q000097:blood / Q000235:genetics / Q000378:metabolism; D020381:Interleukin-17 / Q000097:blood / Q000235:genetics* / Q000378:metabolism; D015847:Interleukin-4 / Q000097:blood / Q000235:genetics / Q000378:metabolism; D007378:Interleukins / Q000097:blood / Q000235:genetics* / Q000378:metabolism; D016410:Lymphoma, T-Cell, Cutaneous / Q000097:blood / Q000235:genetics* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D010766:Phosphorylation; D054399:Receptors, CCR6 / Q000097:blood / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D050796:STAT3 Transcription Factor / Q000378:metabolism; D012867:Skin / Q000378:metabolism / Q000473:pathology; D012878:Skin Neoplasms / Q000097:blood / Q000235:genetics* / Q000378:metabolism; D059016:Tumor Microenvironment / Q000235:genetics; D000097043:Interleukin-22
chemical_list: D054418:Chemokine CCL20; D016753:Interleukin-10; D020381:Interleukin-17; D015847:Interleukin-4; D007378:Interleukins; D054399:Receptors, CCR6; D050796:STAT3 Transcription Factor; D000097043:Interleukin-22; C108355:CCL20 protein, human; C106311:CCR6 protein, human; C494086:STAT3 protein, human