Excessive CD4+ T cells co-expressing interleukin-17 and interferon-γ in patients with Behçet's disease

Shimizu, Jun; Takai, Kenji; Fujiwara, Naruyoshi; Arimitsu, Nagisa; Ueda, Y.; Wakisaka, Sueshige; Yoshikawa, Hideshi; Kaneko, Fumio; Suzuki, Tomoko; Suzuki, Noboru

doi:10.1111/j.1365-2249.2011.04543.x

Cited by 90 publications

(52 citation statements)

References 39 publications

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“…Because anti-IL-17 and anti-p19 Abs target two important IL-17-producing T cell subsets, namely Th17 as well as inflammatory gd T cells, these T cell subsets likely possess key functions in psoriasis, as their blockade also causes successive reduction of Th1 cytokines, such as IFN-g and TNF-a. Consistently, a stimulating effect of IL-17 on IFN-g-producing cells has previously been described in other inflammation models (46,47). The slightly lower efficiency of anti-gdTCR treatment in our depletion experiments may either reflect an insufficient effect of anti-gdTCR on an established Th1 and Th17 cell infiltrate or on other innate immune cells such as IL-22 + Rorgt + ILCs (22), a partially activating effect of the Abs used (48) or a simultaneous elimination of beneficial immunosuppressive gd T cells (49).…”

Section: Discussionsupporting

confidence: 63%

Reduction of CD18 Promotes Expansion of Inflammatory γδ T Cells Collaborating with CD4+ T Cells in Chronic Murine Psoriasiform Dermatitis

Gatzka

Hainzl

Peters

et al. 2013

The Journal of Immunology

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IL-17 is a critical factor in the pathogenesis of psoriasis and other inflammatory diseases. The impact of γδ T cells, accounting for an important source of IL-17 in acute murine IL-23– and imiquimod-induced skin inflammation, in human psoriasis is still unclear. Using the polygenic CD18hypo PL/J psoriasis mouse model spontaneously developing chronic psoriasiform dermatitis due to reduced CD18/β2 integrin expression to 2–16% of wild-type levels, we investigated in this study the influence of adhesion molecule expression on generation of inflammatory γδ T cells and analyzed the occurrence of IL-17–producing γδ and CD4+ T cells at different disease stages. Severity of CD18hypo PL/J psoriasiform dermatitis correlated with a loss of skin-resident Vγ5+ T cells and concurrent skin infiltration with IL-17+, IL-22+, and TNF-α+ γδTCRlow cells preceded by increases in Vγ4+ T cells in local lymph nodes. In vitro, reduced CD18 levels promoted expansion of inflammatory memory-type γδ T cells in response to IL-7. Similar to IL-17 or IL-23/p19 depletion, injection of diseased CD18hypo PL/J mice with anti-γδTCR Abs significantly reduced skin inflammation and largely eliminated pathological γδ and CD4+ T cells. Moreover, CD18hypo γδ T cells induced allogeneic CD4+ T cell responses more potently than CD18wt counterparts and, upon adoptive transfer, triggered psoriasiform dermatitis in susceptible hosts. These results demonstrate a novel function of reduced CD18 levels in generation of pathological γδ T cells that was confirmed by detection of increases in CD18low γδ T cells in psoriasis patients and may also have implications for other inflammatory diseases.

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Section: Discussionsupporting

confidence: 63%

Reduction of CD18 Promotes Expansion of Inflammatory γδ T Cells Collaborating with CD4+ T Cells in Chronic Murine Psoriasiform Dermatitis

Gatzka

Hainzl

Peters

et al. 2013

The Journal of Immunology

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“…This T cell subset has been described previously as playing an important role mediating autoimmune disease. 17 These data demonstrate distinct differences in frequencies of multi-functional T cells between tumor and NTB tissue.…”

Section: Il-2mentioning

confidence: 70%

Functional impairment of infiltrating T cells in human colorectal cancer

et al. 2016

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T cells play a crucial role in preventing the growth and spread of colorectal cancer (CRC). However, immunotherapies against CRC have only shown limited success, which may be due to lack of understanding about the effect of the local tumor microenvironment (TME) on T cell function. The goal of this study was to determine whether T cells in tumor tissue were functionally impaired compared to T cells in non-tumor bowel (NTB) tissue from the same patients. We showed that T cell populations are affected differently by the TME. In the tumor, T cells produced more IL-17 and less IL-2 per cell than their counterparts from NTB tissue. T cells from tumor tissue also had impaired proliferative ability compared to T cells in NTB tissue. This impairment was not related to the frequency of IL-2 producing T cells or regulatory T cells, but T cells from the TME had a higher co-expression of inhibitory receptors than T cells from NTB. Overall, our data indicate that T cells in tumor tissue are functionally altered by the CRC TME, which is likely due to cell intrinsic factors. The TME is therefore an important consideration in predicting the effect of immune modulatory therapies.

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“…Th17 cells, an effector population of Th cells that produce IL-17, have also been implicated recently in BD. Thus, increased frequencies of Th17 cells as well as interferon (IFN)-g expressing Th17 cells have been reported in the skin lesions of patients with BD compared to healthy controls [44]. Another study demonstrated that in active BD the percentage of circulating Th17 cells and plasma interleukin (IL)-17A levels were increased [45].…”

Section: Th17 and Cytokine Involvementmentioning

confidence: 99%

Is Behçet's disease a ‘class 1-opathy’? The role of HLA-B*51 in the pathogenesis of Behçet's disease

Giza

Koftori

Chen

et al. 2017

Clinical and Experimental Immunology

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Summary The association between carriage of the human leucocyte antigen (HLA)-B*51 allele and development of Behçet's disease (BD) has been known since the early 1970s, but the exact mechanisms responsible for its role in pathogenesis remain much-debated. In an effort to explain the disease process, it has been suggested that BD constitutes one of a newly termed group of diseases, the ‘MHC-I-opathies’. Other MHC-I-opathies include ankylosing spondylitis and HLA-B*27-associated spondyloarthropathies and HLA-C*0602-associated skin psoriasis. Recent work analysing the peptidome of HLA-B*51 suggests that altered peptide presentation by HLA-B*51 is vital to the disease process. In this review, we argue that immune receptor interactions with HLA-B*51 or the HLA-B*51-peptide complex could lead to development of inflammation in BD. The evidence for CD8+ T cell involvement is weak, and based on emerging studies it seems more likely that natural killer (NK) or other cell interactions, perhaps mediated by leucocyte immunoglobulin-like receptor (LILR) or killer immunoglobulin-like receptor (KIR) receptors, are culpable in pathogenesis. HLA misfolding leading directly to inflammation is another hypothesis for BD pathogenesis that deserves greater investigation. Ultimately, greater understanding of HLA-B*51's unique role in BD will probably lead to improved development of therapeutic strategies.

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Excessive CD4+ T cells co-expressing interleukin-17 and interferon-γ in patients with Behçet's disease

Abstract: SummaryExcessive T helper type 1 (Th1) cell activity has been reported in Behçet's disease (BD). Recently, association of Th17 cells with certain autoimmune diseases was reported, and we thus investigated circulating Th17 cells in BD.

Cited by 90 publications

References 39 publications

Reduction of CD18 Promotes Expansion of Inflammatory γδ T Cells Collaborating with CD4+ T Cells in Chronic Murine Psoriasiform Dermatitis

Reduction of CD18 Promotes Expansion of Inflammatory γδ T Cells Collaborating with CD4+ T Cells in Chronic Murine Psoriasiform Dermatitis

Functional impairment of infiltrating T cells in human colorectal cancer

Is Behçet's disease a ‘class 1-opathy’? The role of HLA-B*51 in the pathogenesis of Behçet's disease

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