IL-17 and Th17 cells in systemic sclerosis: a comprehensive review

Bălănescu, Paul; Bălănescu, Eugenia; Balanescu, A.

doi:10.1515/rjim-2017-0027

Cited by 13 publications

(22 citation statements)

References 38 publications

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“…In SSc, the mRNA and protein expression of IL17A was found to be positively correlated to an outcome index, the modified Rodnan skin score 17,19 .…”

Section: Introductionmentioning

confidence: 98%

“…The retinoic acid receptor-related-orphan- receptor-gamma T (RORγT), is the key transcription factor required for TH17 cell differentiation and for production of cytokines which participates in protective immunity at boundary tissues 15 . IL17A primarily binds to IL-17RA 16 and initiates a pro-inflammatory signal, which is strongly involved in the progression of many autoimmune diseases in humans 17,18 .…”

Section: Introductionmentioning

confidence: 99%

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TH17 cells expressing CD146 are significantly increased in patients with Systemic sclerosis

Gabsi

Heim

Dlala

et al. 2019

Sci Rep

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Systemic sclerosis (SSc) is an autoimmune disorder characterized by vascular damage, excessive fibrosis and abnormal T cells immune-regulation. CD146 is an adhesion molecule essentially expressed in the vascular system, but also on TH17 lymphocytes. In view of the recently described role of CD146 in SSc, we hypothesized an involvement of CD146 positive TH17 cells in this disease. Compared to healthy controls, we showed that both soluble form of CD146 (sCD146), and IL17A levels were increased in patients with SSc with a positive correlation between both factors. A significant increase in TH17 cells attested by an increase of RORγT, IL17A mRNA and CD4+ IL17A+ cell was observed in patients with SSc. Interestingly, the percentage of TH17 cells expressing CD146 was higher in patients with SSc and inversely correlated with pulmonary fibrosis. In vitro experiments showed an augmentation of the percentage of TH17 cells expressing CD146 after cell treatment with sCD146, suggesting that, in patients the increase of this sub-population could be the consequence of the sCD146 increase in serum. In conclusion, TH17 cells expressing CD146 could represent a new component of the adaptive immune response, opening the way for the generation of new tools for the management of SSc.

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“…In SSc, the mRNA and protein expression of IL17A was found to be positively correlated to an outcome index, the modified Rodnan skin score 17,19 .…”

Section: Introductionmentioning

confidence: 98%

Section: Introductionmentioning

confidence: 99%

TH17 cells expressing CD146 are significantly increased in patients with Systemic sclerosis

Gabsi

Heim

Dlala

et al. 2019

Sci Rep

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“…As regards cell-mediated immunity, a relevant role of T lymphocyte responses and pro-inflammatory cytokine aberrant production in the pathogenesis of SSc has been highlighted, with their possible contribution in the modulation of fibrosis and vascular damage [ 17 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 ]. Recent data from our group support the importance of HCMV specific CD8+ T cells, demonstrating a statistically significant association of HCMV-antigen driven CD8+ T cell responses in SSc patients with some of the most relevant disease parameters [ 16 ].…”

Section: Introductionmentioning

confidence: 99%

Impact of Human Cytomegalovirus and Human Herpesvirus 6 Infection on the Expression of Factors Associated with Cell Fibrosis and Apoptosis: Clues for Implication in Systemic Sclerosis Development

Arcangeletti

D’Accolti

Maccari

et al. 2020

IJMS

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Systemic sclerosis (SSc) is a severe autoimmune disorder characterized by vasculopathy and multi-organ fibrosis; its etiology and pathogenesis are still largely unknown. Herpesvirus infections, particularly by human cytomegalovirus (HCMV) and human herpesvirus 6 (HHV-6), have been suggested among triggers of the disease based on virological and immunological observations. However, the direct impact of HCMV and/or HHV-6 infection on cell fibrosis and apoptosis at the cell microenvironment level has not yet been clarified. Thus, this study aimed to investigate the effects of HCMV and HHV-6 infection on the induction of pro-fibrosis or pro-apoptosis conditions in primary human dermal fibroblasts, one of the relevant SSc target cells. The analysis, performed by microarray in in vitro HCMV- or HHV-6-infected vs. uninfected cells, using specific panels for the detection of the main cellular factors associated with fibrosis or apoptosis, showed that both viruses significantly modified the expression of at least 30 pro-fibrotic and 20 pro-apoptotic factors. Notably, several recognized pro-fibrotic factors were highly induced, and most of them were reported to be involved in vivo in the multifactorial and multistep pathogenic process of SSc, thus suggesting a potential role of both HCMV and HHV-6.

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“…Th-17 cells are known to be primarily involved in inflammatory processes underlying SSc pathogenesis [ 29 ] and high levels of serum and tissue IL-17 have been associated with skin and lung fibrosis in SSc [ 17 , 30 ].…”

Section: Discussionmentioning

confidence: 99%

Gastric Juice Expression of Th-17 and T-Reg Related Cytokines in Scleroderma Esophageal Involvement

Nicola¹,

Rolla²,

Bucca³

et al. 2020

Cells

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Background: Systemic sclerosis (SSc) is a connective tissue disorder which key feature is a fibrotic process. The role of Endothelin-1 (ET-1) and T-helper (Th)-1 cells in lung and skin fibrosis is well known, although Th17- and Treg-cells were found to be involved. However, no studies analyzed cytokines expression in gastric-juice of SSc patients. Our study aimed to evaluate proinflammatory and profibrotic cytokines in gastric-juice of SSc patients and to investigate their correlations with esophageal dysmotility. Methods: Patients performed upper-gastrointestinal-endoscopy with gastric-juice collection, esophageal manometry and thoracic CT-scan. GM-CSF, ET-1, Th-1 (IFN-γ, IL-1β, TNF-α, IL-2, IL-6, IL-9), Th-17 (IL-17, IL-21, IL-22, IL-23) and T-reg (IL-10, TGF-β) related cytokines were measured in 29 SSc-patients and 20 healthy-controls. Results: Patients showed significant lower levels of IL-6, IL-17, IL-22 and ET-1 (p < 0.005) compared with controls. Patients with atrophic gastritis presented significant lower levels of IL-2, IL-9, IL-6, TGF-β, GM-CSF, IL-17 and ET-1 (p < 0.005) compared to patients without gastritis. Increased values of IL-2, IL-9, IL-1β, IL-17, ET-1 and GM-CSF (p < 0.005) were observed in patients with esophageal impairment. This is the first report of cytokines measurement in gastric juice of patients with SSc. The high IL-17 concentrations in gastric-juice of scleroderma patients with esophageal dysmotility support the signature of Th-17 cells in scleroderma esophageal fibrosis.

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IL-17 and Th17 cells in systemic sclerosis: a comprehensive review

Cited by 13 publications

References 38 publications

TH17 cells expressing CD146 are significantly increased in patients with Systemic sclerosis

TH17 cells expressing CD146 are significantly increased in patients with Systemic sclerosis

Impact of Human Cytomegalovirus and Human Herpesvirus 6 Infection on the Expression of Factors Associated with Cell Fibrosis and Apoptosis: Clues for Implication in Systemic Sclerosis Development

Gastric Juice Expression of Th-17 and T-Reg Related Cytokines in Scleroderma Esophageal Involvement

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