Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2010 May;130(5):1373-83.
doi: 10.1038/jid.2009.399. Epub 2009 Dec 24.

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

Shinji Kagami  1 , Heather L Rizzo, Jennifer J Lee, Yoshinobu Koguchi, Andrew Blauvelt
Affiliations

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

Shinji Kagami et al. J Invest Dermatol. 2010 May.

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.

PubMed Disclaimer

Figures

Figure 1
Figure 1. Circulating CCR6+, IL-23R+, and CD161 + cells are increased in psoriasis
(a) The percentage of CD4+cells expressing CCR6, IL-23R, and CD161 among unstimulated cells from 17 healthy individuals and 21 untreated psoriatics (horizontal bars, mean; each circle, single donor). (b) Representative dot plot analyses of CCR6, IL-23R, and CD161 expression in circulating unstimulated CD4+ cells from the same individual. (c)The percentages of each subset divided by the total number of circulating CCR6, IL-23R, and CD161-positive cells in unstimulated CD4+cells of healthy individuals (white bars) and psoriatics (black bars). Data expressed as mean ± SD; *P < 0.05, **P < 0.01, and ***P < 0.001.
Figure 2
Figure 2. Circulating Th17, Th1, and Th17/Th1 cells are increased in psoriasis
(a)In single-color flow analyses, circulating IL-17A+, IL-22+, IFN-g+, and tumor necrosis factor (TNF)-alpha + cells are increased in psoriasis patients. (b)Representative two-color dot plot analyses of IL-17A and IFN-γ expression in stimulated CD4+ cells from a healthy volunteer and a psoriasis patient. (c)The percentages of circulating Th17 (IL-17A + IFN-γ−), Th1 (IL-17A−IFN-γ+), and Th17/Th1 (IL-17A + IFN-γ+) cells among stimulated CD4+ cells from healthy individuals and psoriatics. For a and c, each circle, single donor; horizontal bars, mean; and *P < 0.05, **P < 0.01, and ***P < 0.001.
Figure 3
Figure 3. Most Th17 cells do not simultaneously express both IL-17A and IL-22
(a)Representative two-color dot plot analyses of IL-17A, IL-22, and IFN-γ expression in stimulated CD4+ cells from a single patient with psoriasis. (b)The percentages of circulating CD4+ cells that coexpress IL-17A, IL-22, and IFN-γ in healthy individuals (white bars) and psoriatics (black bars). Data expressed as mean ± SD; *P<0.05, **P<0.01, and ***P<0.001.
Figure 4
Figure 4. On the basis of IL-17A production, CCR6 is a more reliable cell surface marker for Th17 cells when compared with IL-23R or CD161
IL-17A + cells, IL-22 + cells, and IFN-γ + cells from psoriatics were gated and the percentage of cells coexpressing CCR6, IL-23R, CD161, or tumor necrosis factor (TNF)-α was determined (black bars). Similarly, IL-17A− cells, IL-22− cells, and IFN-γ− cells from psoriatics were gated and the percentage of cells coexpressing CCR6, IL-23R, CD161, or TNF-α was determined (white bars). Data expressed as mean ± SD; NS, not significant; *P < 0.05, **P < 0.01, and ***P < 0.001.
Figure 5
Figure 5. CCR6 + IL-17A+, CCR6 + IL-22+, and CCR6 + TNF-α+ cells are increased in psoriatics compared with healthy individuals
Representative two-color dot plot analyses of CCR6 and IL-17A/IL-22/tumor necrosis factor (TNF)-α expression in stimulated CD4+ cells from a single healthy volunteer (a) and a psoriasis patient (b).(c)The percentages of circulating IL-17A +cells that coexpress CCR6, IL-23R, and CD161 among stimulated CD4+ cells from healthy individuals and psoriatics. (d)The percentages of circulating IL-22 +cells that coexpress CCR6, IL-23R, and CD161 among stimulated CD4+ cells from healthy individuals and psoriatics. (e)The percentages of circulating TNF-α+ cells that coexpress CCR6, IL-23R, and CD161 among stimulated CD4+ cells from healthy individuals and psoriatics. Each circle, single donor; horizontal bars, mean; *P < 0.05, **P < 0.01, and ***P < 0.001.
Figure 6
Figure 6. NF-κB and STAT3 inhibition in vitro blocks cytokine production by both Th17 and Th1 cells in a dose-dependent manner
(a) CD4+ cells were cultured overnight with or without parthenolide or stattic at the indicated concentrations, and then activated with phorbol myristate acetate (PMA)/ionomycin for 6 hours. Representative two-color dot plot analyses of IFN-γ and tumor necrosis factor (TNF)-α expression from a single healthy volunteer are shown. (b)The percentage of circulating CD4+ cells producing IL-17A, IL-22, IFN-γ, and TNF-α in healthy individuals (solid lines) and psoriatics (dotted lines) with or without 2.5 µm of parthenolide or 1 µm of stattic. Each line, single donor.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Acosta-Rodriguez EV, Rivino L, Geginat J, et al. Surface phenotype and antigenic specificity of human interleukin 17-producing T helper memory cells. Nat Immunol. 2007;8:639–646. - PubMed
    1. Annunziato F, Cosmi L, Santarlasci V, et al. Phenotypic and functional features of human Th17 cells. J Exp Med. 2007;204:1849–1861. - PMC - PubMed
    1. Arican O, Aral M, Sasmaz S, et al. Serum levels of TNF-alpha, IFN-gamma, IL-6, IL-8, IL-12, IL-17, and IL-18 in patients with active psoriasis and correlation with disease severity. Mediators Inflamm. 2005;2005:273–279. - PMC - PubMed
    1. Austin LM, Ozawa M, Kikuchi T, et al. The majority of epidermal T cells in psoriasis vulgaris lesions can produce type 1 cytokines, interferon-gamma, interleukin-2, and tumor necrosis factor-alpha, defining TC1 (cytotoxic T lymphocyte) and TH1 effector populations: a type 1 differentiation bias is also measured in circulating blood T cells in psoriatic patients. J Invest Dermatol. 1999;113:752–759. - PubMed
    1. Boyman O, Hefti HP, Conrad C, et al. Spontaneous development of psoriasis in a new animal model shows an essential role for resident T cells and tumor necrosis factor-alpha. J Exp Med. 2004;199:731–736. - PMC - PubMed

Publication types

MeSH terms