Circulating Th17, Th22, and Th1 cells are increased in psoriasis.
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.
Kagami
Shinji
S
Department of Dermatology, Oregon Health and Science University, Portland, Oregon, USA.
Rizzo
Heather L
HL
Lee
Jennifer J
JJ
Koguchi
Yoshinobu
Y
Blauvelt
Andrew
A
D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D015415:Biomarkers / Q000378:metabolism; D015704:CD4 Antigens / Q000378:metabolism; D018791:CD4 Lymphocyte Count; D003879:Dermatologic Agents / Q000627:therapeutic use; D005434:Flow Cytometry; D006801:Humans; D000069285:Infliximab; D020381:Interleukin-17 / Q000097:blood*; D007378:Interleukins / Q000097:blood*; D016328:NF-kappa B / Q000378:metabolism; D055651:NK Cell Lectin-Like Receptor Subfamily B / Q000378:metabolism; D011565:Psoriasis / Q000188:drug therapy / Q000276:immunology* / Q000473:pathology; D054399:Receptors, CCR6 / Q000378:metabolism; D018123:Receptors, Interleukin / Q000378:metabolism; D050796:STAT3 Transcription Factor / Q000378:metabolism; D012720:Severity of Illness Index; D018417:Th1 Cells / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D000097043:Interleukin-22
D000911:Antibodies, Monoclonal; D015415:Biomarkers; D015704:CD4 Antigens; D003879:Dermatologic Agents; D000069285:Infliximab; D020381:Interleukin-17; D007378:Interleukins; D016328:NF-kappa B; D055651:NK Cell Lectin-Like Receptor Subfamily B; D054399:Receptors, CCR6; D018123:Receptors, Interleukin; D050796:STAT3 Transcription Factor; D014409:Tumor Necrosis Factor-alpha; D000097043:Interleukin-22; C106311:CCR6 protein, human; C508717:IL17A protein, human; C515500:IL23R protein, human; C527203:KLRB1 protein, human; C494086:STAT3 protein, human