Lesional Th17 cells and regulatory T cells in bullous pemphigoid

Arakawa, Masataka; Dainichi, Teruki; Ishii, Norito; Hamada, Takahiro; Karashima, Tadashi; Nakama, Takekuni; Yasumoto, Shinichiro; Tsuruta, Daisuke; Hashimoto, Takashi

doi:10.1111/j.1600-0625.2011.01378.x

Cited by 98 publications

(108 citation statements)

References 14 publications

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“…Indeed, patients with rheumatoid arthritis demonstrated a significant Treg increase in synovial fluid suggesting that recruitment to inflammatory sites may be responsible for circulating Treg reduction [23]. This phenomenon has not been demonstrated in BP, as the recent data by Arakawa et al [4] showed a significant reduction in FOXP3+ cells in BP lesional skin compared with pemphigus vulgaris. As to the effective functional properties of these cells, the phenotypic characterisation performed in our study can give some more insights.…”

Section: Discussionmentioning

confidence: 57%

Circulating CD4+ CD25brightFOXP3+ regulatory T-cells are significantly reduced in bullous pemphigoid patients

et al. 2012

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Bullous pemphigoid (BP) is the most frequent autoimmune bullous skin disease, characterised by autoantibodies against the hemidesmosome complex. Recently, regulatory T cells (Tregs) have been implicated in the development of several autoimmune diseases; few data are available in BP, failing to demonstrate a role of this subset in disease pathogenesis. The aim of this study was to investigate the expression and phenotypes of different Tregs (CD4+ CD25brightFOXP3+ and CD8+ CD28-cells) in BP to clarify whether the depletion of this subset constitutes one mechanism of tolerance loss. The CD4+ CD25bright-FOXP3 and CD8+ CD28-circulating subsets were determined by flow-cytometry in 26 untreated BP patients and compared with a group of age-and sex-matched healthy controls (HC, n = 30). Absolute and percentage values of the CD4+ CD25brightFOXP3+ cells were significantly reduced in BP compared with HC (median CD25bright-FOXP3+ expression within CD4+ cells: 1.8 vs. 3.5%, p = 0.002); conversely, BP patients were characterised by a significant expansion of the CD25brightFOXP3-''activated'' T-cell subset. CCR4 and CD62L were expressed on the majority of CD4+ CD25brightFOXP3+ cells (75.2 and 82.3%, respectively). No differences in the CD8+ CD28-subset were found between BP and HC. This is the first report showing a significant reduction of circulating CD4+ CD25brightFOXP3+ Treg frequency in BP patients.

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Section: Discussionmentioning

confidence: 57%

Circulating CD4+ CD25brightFOXP3+ regulatory T-cells are significantly reduced in bullous pemphigoid patients

et al. 2012

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“…Besides T h 17 cells, it has to be mentioned that several innate immune cell type such as innate lymphoid cells (NK and γδ T cells), neutrophils and mast cells can also produce IL-17 in inflammatory conditions (Cua and Tato 2010)(Lin et al 2011)(Keijsers et al 2013). In BP, some recent studies using immunohistochemical approaches have suggested the presence of T h 17 cells at site of the dermal-epidermal detachment (Arakawa et al 2011)(Fischer-Stabauer et al 2012)(Zebrowska et al 2013). Although T h 17 cells are characterized by their ability to produce high level of IL-17 (Harrington et al 2005)(Park et al 2005), the mechanisms conducting to IL-17 production and its link with blister formation are still unraveled in BP.…”

Section: Introductionmentioning

confidence: 99%

Innate Immune Cell–Produced IL-17 Sustains Inflammation in Bullous Pemphigoid

Jan

Plée

Vallerand

et al. 2014

Journal of Investigative Dermatology

102

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Bullous pemphigoid (BP) is an autoimmune skin disease characterized by the binding of autoantibodies to components of the hemidesmosome structure resulting in an inflammatory response and subepidermal blister formation. To investigate the role of immune orientation in the inflammatory processes associated to disease progression, blister fluid, serum and biopsy specimens were collected from thirty one consecutive BP patients. Blister fluids displayed high level of IL-6, IL-17, IL-22, IL-23, whereas TGF-β was increased in BP sera. However neither immunocytochemistry on a trans-differentiation model of IL-17-producing PBMCs nor immunohistochemistry on BP biopsy specimens could demonstrate the presence of Th17 lymphocytes. Instead innate immune cells, especially neutrophils, produced IL-17 at the skin lesional site. Of note, superpotent topical corticosteroid application quickly and dramatically reduced both IL-17 expression and clinical signs of BP. Consistently, IL-17 upregulated MMP-9 and neutrophil elastase expression, two proteases involved in blister formation, thereof further demonstrating its role in the progress of BP. Finally IL-17-induced matrix degradation originated from neutrophil activation, initiated the formation of an amplification loop of the inflammatory response that could represent the underlying phenomenon leading to the maintenance and even disease extent. Thus, our results could open new therapeutic strategies for BP patients.

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“…Th17'den salınan IL-17A; multipl proinflamatuvar mediatörleri etkileyerek etkisini gösteren bir sitokindir 10 . Th17 hücre aracılı inflamasyonla ilişkili olarak otoimmün büllöz hastalıklar arasından büllöz pemfigoid ile ilişkisinin daha güçlü olduğuna dair kanıtlar mevcuttur 23,24 . Yaptığımız literatür taramalarında Th17 hücrelerden salınan IL-17A'nın PV ile ilişkisini araştıran çok fazla çalışmaya rastlamadık.…”

Section: Discussionunclassified

Analysis of serum cytokine levels in patients with pemphigus vulgaris

Uçmak¹,

Akkurt²,

Yüksel³

et al. 2015

TURKDERM

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Background and Design: Pemphigus vulgaris (PV) is an autoimmune blistering skin disease. The aim of this study was to compare the levels of T helper 1 (Th1), T helper 2 (Th2) and T helper 17 (Th17) type cytokines in PV patients and healthy controls. Materials and Methods: The study population included 37 patients with PV and 35 healthy individuals. The patients were grouped into mild, moderate and severe disease groups according to the severity of skin and mucosal involvement. Serum interleukin (IL)-2, IL-4, IL-6, IL-8, IL-10, IL-12, IL-17A and interferon (IFN)-γ levels were assessed using the enzyme-linked immunosorbent assay method. Serum cytokine levels were compared between patients and controls and between patient subgroups. Analysis of data was done using SPSS 15.0. Results: Serum IL-2, IL-4, IL-6 levels were significantly higher in the patient group compared to the control group (p<0.001, p<0.001, p<0.001, respectively). IL-6 levels were found to be correlated with the severity of disease (r=0.490, p=0.003). There was no statistically significant difference in serum cytokine levels between the patient subgroups. Conclusion: Th2 type cytokines were found to be increased in serum of patients with pemphigus vulgaris. These results support that the Th2 cytokine response plays a major role in the etiopathogenesis of pemphigus vulgaris. (Turkderm 2015; 49: 25-30)

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Lesional Th17 cells and regulatory T cells in bullous pemphigoid

Cited by 98 publications

References 14 publications

Circulating CD4+ CD25brightFOXP3+ regulatory T-cells are significantly reduced in bullous pemphigoid patients

Circulating CD4+ CD25brightFOXP3+ regulatory T-cells are significantly reduced in bullous pemphigoid patients

Innate Immune Cell–Produced IL-17 Sustains Inflammation in Bullous Pemphigoid

Analysis of serum cytokine levels in patients with pemphigus vulgaris

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