title: Deficient cutaneous antibacterial competence in cutaneous T-cell lymphomas: role of Th2-mediated biased Th17 function.
abstract: OBJECTIVE
  Primary cutaneous T-cell lymphomas (CTCL) are neoplastic disorders of skin-homing T cells. Affected skin areas show morphologic similarities with alterations in other T-cell-mediated dermatoses. Furthermore, as in atopic dermatitis but in contrast with psoriasis, patients with CTCL are frequently afflicted by cutaneous bacterial infections that support the survival of lymphoma cells. Our aim was to investigate the mechanisms of elevated susceptibility to cutaneous infections in patients with CTCL.
  
  
  METHODS
  Skin samples from CTCL, psoriasis, and atopic dermatitis patients were used to illuminate the antibacterial competence status and the presence of its modulating cytokines. For substantiation of findings, 3-dimensional epidermis models, isolated and in vitro generated Th-subpopulations, were applied. Parameters were analyzed via qPCR and IHC.
  
  
  RESULTS
  CTCL lesions compared with psoriatic lesions presented an impaired upregulation of antibacterial proteins (ABPs), with levels even below those in atopic dermatitis. This was associated with a relative deficiency of the ABP-inducing cytokine IL-17 and a strong presence of the ABP-downregulating cytokine IL-13. The simultaneous presence of the Th17-cell cytokine IL-26 indicated that IL-17 deficiency in CTCL lesions results from functional deviation of Th17 cells. Accordingly, IL-17 but not IL-26 production by Th17 cells in vitro was inhibited by IL-4Rα ligand. Levels of other ABP inducers were comparable between CTCL and psoriasis lesions. The same was true about IL-22/TNF-α targets, including the keratinocyte hyper-regeneration marker K16 and the matrix-degrading enzyme MMP1.
  
  
  CONCLUSIONS
  Our results suggest that the cutaneous bacterial infections in CTCL are caused by impaired ABP induction as consequence of Th2-mediated biased Th17-cell function.
authors.affiliation: Psoriasis Research and Treatment Center, University Hospital Charité, Berlin, Germany. Interdisciplinary Group of Molecular Immunopathology, Dermatology/Medical Immunology, University Hospital Charité, Berlin, Germany. Research Center Immunosciences, University Hospital Charité, Berlin, Germany.
authors.forename: Kerstin
authors.initials: K
authors.lastname: Wolk
authors.affiliation: Laboratory for Investigative Dermatology, Rockefeller University, New York, New York.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Mitsui
authors.affiliation: Psoriasis Research and Treatment Center, University Hospital Charité, Berlin, Germany. Interdisciplinary Group of Molecular Immunopathology, Dermatology/Medical Immunology, University Hospital Charité, Berlin, Germany.
authors.forename: Katrin
authors.initials: K
authors.lastname: Witte
authors.affiliation: Department of Dermatology and Allergy, University Hospital Charité, Berlin, Germany.
authors.forename: Sylke
authors.initials: S
authors.lastname: Gellrich
authors.affiliation: Laboratory for Investigative Dermatology, Rockefeller University, New York, New York.
authors.forename: Nicholas
authors.initials: N
authors.lastname: Gulati
authors.affiliation: Department of Dermatology and Allergy, University Hospital Charité, Berlin, Germany.
authors.forename: Daniel
authors.initials: D
authors.lastname: Humme
authors.affiliation: Psoriasis Research and Treatment Center, University Hospital Charité, Berlin, Germany. Interdisciplinary Group of Molecular Immunopathology, Dermatology/Medical Immunology, University Hospital Charité, Berlin, Germany.
authors.forename: Ellen
authors.initials: E
authors.lastname: Witte
authors.affiliation: Interdisciplinary Group of Molecular Immunopathology, Dermatology/Medical Immunology, University Hospital Charité, Berlin, Germany.
authors.forename: Melanie
authors.initials: M
authors.lastname: Gonsior
authors.affiliation: Department of Dermatology and Allergy, University Hospital Charité, Berlin, Germany.
authors.forename: Marc
authors.initials: M
authors.lastname: Beyer
authors.affiliation: Department of Dermatology, Boston University, Roger Williams Medical Center, Providence, Rhode Island.
authors.forename: Marshall E
authors.initials: ME
authors.lastname: Kadin
authors.affiliation: Institute of Medical Immunology, University Hospital Charité, Berlin, Germany. Berlin-Brandenburg Center for Regenerative Therapies, University Hospital Charité, Berlin, Germany.
authors.forename: Hans-Dieter
authors.initials: HD
authors.lastname: Volk
authors.affiliation: Laboratory for Investigative Dermatology, Rockefeller University, New York, New York.
authors.forename: James G
authors.initials: JG
authors.lastname: Krueger
authors.affiliation: Department of Dermatology and Allergy, University Hospital Charité, Berlin, Germany.
authors.forename: Wolfram
authors.initials: W
authors.lastname: Sterry
authors.affiliation: Psoriasis Research and Treatment Center, University Hospital Charité, Berlin, Germany. Interdisciplinary Group of Molecular Immunopathology, Dermatology/Medical Immunology, University Hospital Charité, Berlin, Germany. Research Center Immunosciences, University Hospital Charité, Berlin, Germany. robert.sabat@charite.de.
authors.forename: Robert
authors.initials: R
authors.lastname: Sabat
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000900:Anti-Bacterial Agents / Q000276:immunology*; D002478:Cells, Cultured; D003876:Dermatitis, Atopic / Q000276:immunology; D004817:Epidermis / Q000276:immunology*; D005260:Female; D006801:Humans; D007378:Interleukins / Q000276:immunology; D015603:Keratinocytes / Q000276:immunology; D016410:Lymphoma, T-Cell, Cutaneous / Q000276:immunology*; D008297:Male; D020781:Matrix Metalloproteinase 1 / Q000276:immunology; D008875:Middle Aged; D011565:Psoriasis / Q000276:immunology; D012878:Skin Neoplasms / Q000276:immunology*; D058504:Th17 Cells / Q000276:immunology*; D018418:Th2 Cells / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology
chemical_list: D000900:Anti-Bacterial Agents; D007378:Interleukins; D014409:Tumor Necrosis Factor-alpha; C522360:MMP1 protein, human; D020781:Matrix Metalloproteinase 1