Circulating Th17, Th22, and Th1 cells are increased in psoriasis

J Invest Dermatol. 2010 May;130(5):1373-83. doi: 10.1038/jid.2009.399. Epub 2009 Dec 24.

Abstract

Th17, Th22, and Th1 cells are detected in psoriatic skin lesions and implicated in psoriasis pathogenesis, but inflammatory T cell numbers in blood, as well as the relative importance of each cell type, is unclear. Using 7-color flow cytometry, circulating Th17, Th22, and Th1 cells were quantified in 21 untreated psoriatics and 17 healthy individuals. CCR6 was the best cell surface marker for IL-17A+ cells when compared with IL-23R or CD161. CCR6+, IL-17A+, IL-22+, CCR6+IL-17A+, CCR6+IL-22+, CCR6+tumor necrosis factor-alpha+, IL-17A+IFN-gamma-, IL-17A+IL-22+IFN-gamma-, and IL-17A+IL-22-IFN-gamma- cells were increased in psoriatics (all values P<0.001), indicating elevations in circulating Th17 cells, using multiple criteria to define these cells. Th22 (IL-17A-IL-22+IFN-gamma-, P<0.05) and Th1 (IL-17A-IFN-gamma+, P<0.05) cells were also increased in psoriatics, but to a lesser extent. Inhibition of either NF-kappaB or STAT3 in vitro blocked cytokine production by both Th17 and Th1 cells. Circulating levels of Th17 and Th1 cells decreased in a subset of five psoriasis patients serially evaluated following induction therapy with infliximab. In summary, elevated numbers of circulating inflammatory T cells may contribute to cutaneous inflammation and systemic inflammatory disease that occurs in individuals with psoriasis.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Antibodies, Monoclonal / therapeutic use
  • Biomarkers / metabolism
  • CD4 Antigens / metabolism
  • CD4 Lymphocyte Count
  • Dermatologic Agents / therapeutic use
  • Flow Cytometry
  • Humans
  • Infliximab
  • Interleukin-17 / blood*
  • Interleukins / blood*
  • NF-kappa B / metabolism
  • NK Cell Lectin-Like Receptor Subfamily B / metabolism
  • Psoriasis / drug therapy
  • Psoriasis / immunology*
  • Psoriasis / pathology
  • Receptors, CCR6 / metabolism
  • Receptors, Interleukin / metabolism
  • STAT3 Transcription Factor / metabolism
  • Severity of Illness Index
  • Th1 Cells* / immunology
  • Th1 Cells* / metabolism
  • Th1 Cells* / pathology
  • Tumor Necrosis Factor-alpha / metabolism

Substances

  • Antibodies, Monoclonal
  • Biomarkers
  • CCR6 protein, human
  • CD4 Antigens
  • Dermatologic Agents
  • IL17A protein, human
  • IL23R protein, human
  • Interleukin-17
  • Interleukins
  • KLRB1 protein, human
  • NF-kappa B
  • NK Cell Lectin-Like Receptor Subfamily B
  • Receptors, CCR6
  • Receptors, Interleukin
  • STAT3 Transcription Factor
  • STAT3 protein, human
  • Tumor Necrosis Factor-alpha
  • Infliximab
  • interleukin-22