scholarly journals POS0326 ROLE OF THE IL-25 / IL-17RB AXIS IN TH9 POLARIZATION IN PATIENTS WITH PROGRESSIVE SYSTEMIC SCLEROSIS

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 390-391
Author(s):  
L. La Barbera ◽  
M. Lo Pizzo ◽  
D. DI Liberto ◽  
C. Schinocca ◽  
P. Ruscitti ◽  
...  
Keyword(s):  
Systemic Sclerosis ◽  
Th17 Cells ◽  
Lymphoid Cells ◽  
Healthy Controls ◽  
Significant Group ◽  
Th9 Cells ◽  
Inflammatory Phenotype ◽  
Over Time ◽  
Skin Samples

Background:Systemic sclerosis (SSc) is an inflammatory connective tissue disease leading to chronic and progressive fibrosis, typically affecting the skin and internal organs. The alteration of both innate and adaptive immune responses plays a pivotal role in SSc pathophysiology, although it has not yet been fully elucidated [1].Recent findings have demonstrated interleukin (IL)-9 overexpression and significant group 2 innate lymphoid cells (ILC2) expansion in patients with SSc. Th9-ILC2-mast cells axis seems to be involved in SSc tissue damage and in the induction of fibrosis [2]. Activation and production of IL-9 by Th9 cells are promoted by transforming growth factor (TGF)-β, thymic stromal lymphopoietin (TSLP), IL-25 and IL-33. Thus, the IL-25 / IL-17RB pathway would act as a key player in SSc.Objectives:The purpose of this study was to evaluate the role of the IL-25 / IL-17RB axis as a driver in Th9 polarization and ILC2 expansion and polarization in SSc patients.Methods:26 patients were enrolled in this study. Peripheral blood and skin biopsy specimens were obtained from SSc patients. PBMCs were isolated and incubated with and without recombinant (r)IL-25 for 24-48-72 hours and the frequencies of Th9 cells, Th17 cells and ILC2 were assessed by flow cytometry analysis. Moreover, the ex vivo expression of IL-17RB in ILC2 was also assessed. Immunofluorescence analysis was performed on biopsy skin samples to evaluate IL-17RB expression in ILC2.Results:In SSc samples, Th9 cells frequency progressively increased after stimulation with rIL-25, compared to healthy controls in which IL-9 frequency decreased over time regardless of rIL-25.Simultaneously, we evaluated the role of the IL-25 / IL-17RB axis in Th17 cells.In the SSc pool, the initially low rate of IL-17 increased at 72 hours after stimulation with rIL-25. In unstimulated SSc samples, the initially higher IL-17 rate decreased at 72 hours; conversely, it was consistently low in healthy controls, at both baseline and stimulated conditions.Our results confirmed the presence of IL-25-dependent clonal ILC2 expansion, suggesting a greater and progressive expansion over time in patients with SSc, compared to controls.Interestingly, increased IL-17RB expression was found in circulating ILC2 from SSc patients supporting the characterization of ILC2 inflammatory phenotype.Consistently, immunofluorescence on the skin of SSc patients showed a marked infiltrate of CD3-GATA3+ IL-17RB+ cells, confirming the presence of the activated inflammatory phenotype ILC2, absent in skin biopsies of healthy controls (Figure 1).Conclusion:These preliminary data suggest an active role of the IL-25/IL-17RB axis in SSc. It results in Th9 polarization and Th17 clonal expansion, inducing the production of IL-9 and, to a lesser extent, IL-17. Moreover, in addition to promoting Th9-mediated ILC2 differentiation, IL-25 directs the polarization of ILC2 towards the inflammatory phenotype.References:[1]Denton CP, & Khanna D. (2017). Systemic sclerosis. Lancet (London, England), 390(10103), 1685–1699.[2]Guggino G, Ciccia F, Di Liberto D, Lo Pizzo M, Ruscitti P, Cipriani P, Ferrante A, Sireci G, Dieli F, Fourniè JJ, Giacomelli R, Triolo G. s.l. Interleukin-9 over-expression and T helper 9 polarization in systemic sclerosis patients. Clin Exp Immunol, 2016 Dec.Figure 1.Immunofluorescence on biopsy skin samples of SSc patients (top) and healthy control (bottom).Disclosure of Interests:Lidia La Barbera: None declared, Marianna Lo Pizzo: None declared, Diana Di Liberto: None declared, Claudia Schinocca: None declared, Piero Ruscitti Consultant of: Pfizer, Novartis, Roche, Lilly, Celgene, Abbvie, Rorberto Giacomelli Consultant of: Pfizer, Novartis, Roche, Lilly, Celgene, Abbvie, Francesco Dieli: None declared, francesco ciccia Consultant of: Pfizer, Novartis, Roche, Lilly, Celgene, Abbvie, Giuliana Guggino Consultant of: Pfizer, Novartis, Roche, Lilly, Celgene, Abbvie

scholarly journals ILC1s and ILC3s Exhibit Inflammatory Phenotype in Periodontal Ligament of Periodontitis Patients

2021 ◽  
Vol 12 ◽  
Author(s):  
Changyi Li ◽  
Jianyue Liu ◽  
Jie Pan ◽  
Yuhui Wang ◽  
Lei Shen ◽  
...  
Keyword(s):  
Immune Responses ◽  
Periodontal Ligament ◽  
Inflammatory Diseases ◽  
Innate Lymphoid Cells ◽  
Lymphoid Cells ◽  
Mucosal Barrier ◽  
Healthy Controls ◽  
Inflammatory Phenotype ◽  
Ifn Γ

Innate lymphoid cells (ILCs) are emerging as important players in inflammatory diseases. The oral mucosal barrier harbors all ILC subsets, but how these cells regulate the immune responses in periodontal ligament tissue during periodontitis remains undefined. Here, we show that total ILCs are markedly increased in periodontal ligament of periodontitis patients compared with healthy controls. Among them, ILC1s and ILC3s, particularly NKp44+ILC3 subset, are the predominant subsets accumulated in the periodontal ligament. Remarkably, ILC1s and ILC3s from periodontitis patients produce more IL-17A and IFN-γ than that from healthy controls. Collectively, our results highlight the role of ILCs in regulating oral immunity and periodontal ligament inflammation and provide insights into targeting ILCs for the treatment of periodontitis.

HLA-G Expression in the Skin of Patients with Systemic Sclerosis

2009 ◽  
Vol 36 (6) ◽  
pp. 1230-1234 ◽  
Author(s):  
ISABELA J. WASTOWSKI ◽  
PERCIVAL D. SAMPAIO-BARROS ◽  
ELIANE M.I. AMSTALDEN ◽  
GUSTAVO MARTELLI PALOMINO ◽  
JOÃO FRANCISCO MARQUES-NETO ◽  
...  
Keyword(s):  
Systemic Sclerosis ◽  
Control Sample ◽  
Healthy Controls ◽  
Skin Disorders ◽  
Disease Prognosis ◽  
Laboratory Variables ◽  
Skin Biopsies ◽  
Dermal Cells

Objective.To determine HLA-G expression in skin biopsies from patients with systemic sclerosis (SSc), and its association with epidemiological, clinical, and laboratory variables and survival.Methods.Paraffin-embedded skin biopsies obtained from 21 SSc patients (14 limited SSc, 7 diffuse SSc) and from 28 healthy controls were studied. HLA-G expression was evaluated by immunohistochemistry.Results.HLA-G molecules were detected in 57% of skin biopsies from patients with SSc (9 from limited SSc, 3 from diffuse SSc), whereas no control sample expressed HLA-G (p = 0.000004). In patients, HLA-G molecules were consistently observed within epidermal and some dermal cells. HLA-G expression was associated with a lower frequency of vascular cutaneous ulcers (p = 0.0004), telangiectasias (p = 0.008), and inflammatory polyarthralgia (p = 0.02). After a 15-year followup, SSc patients who exhibited HLA-G survived longer than patients who did not.Conclusion.HLA-G is expressed in skin biopsies from patients with SSc, and this is associated with a better disease prognosis. This suggests a modulatory role of HLA-G in SSc, as observed in other skin disorders.

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

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Amira Gabsi ◽  
Xavier Heim ◽  
Akram Dlala ◽  
Asma Gati ◽  
Haifa Sakhri ◽  
...  
Keyword(s):  
Systemic Sclerosis ◽  
Th17 Cells ◽  
Vascular System ◽  
Adaptive Immune Response ◽  
Autoimmune Disorder ◽  
Soluble Form ◽  
Adaptive Immune ◽  
Th17 Lymphocytes

AbstractSystemic 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.

Evaluation of a Shared Autoimmune Disease-associated Polymorphism of TRAF6 in Systemic Sclerosis and Giant Cell Arteritis

2012 ◽  
Vol 39 (6) ◽  
pp. 1275-1279 ◽  
Author(s):  
F. DAVID CARMONA ◽  
AURORA SERRANO ◽  
LUIS RODRÍGUEZ-RODRÍGUEZ ◽  
JOSÉ LUIS CALLEJAS ◽  
CARMEN P. SIMEÓN ◽  
...  
Keyword(s):  
Systemic Sclerosis ◽  
Giant Cell Arteritis ◽  
Giant Cell ◽  
Lupus Erythematosus ◽  
Genetic Network ◽  
Healthy Controls ◽  
Nucleotide Polymorphism ◽  
Common Risk Factor ◽  
Single Nucleotide

Objective.We evaluated whether a single-nucleotide polymorphism (SNP) of theTRAF6gene previously associated with systemic lupus erythematosus and rheumatoid arthritis may be a common risk factor for systemic sclerosis (SSc) and giant cell arteritis (GCA).Methods.A total of 1185 patients with SSc, 479 patients with biopsy-proven GCA, and 1442 unrelated healthy controls of white Spanish origin were genotyped for the rs540386 variant using a specifically designed TaqMan©allele discrimination assay.Results.No significant associations of this SNP with global SSc or GCA were found. This was also the case when the potential associations of theTRAF6polymorphism with the main clinical phenotypes of the 2 diseases (e.g., limited cutaneous and diffuse cutaneous SSc, or presence of polymyalgia rheumatica and visual ischemic manifestations in GCA) were assessed.Conclusion.Our data do not support a role of the rs540386TRAF6variant as a key component of the genetic network underlying SSc and GCA.

scholarly journals Role of Th9 cells and Th17 cells in the pathogenesis of malignant ascites

2015 ◽  
Vol 5 (10) ◽  
pp. 806-811 ◽  
Author(s):  
Xian-Wen Yang ◽  
Hai-Xing Jiang ◽  
Xiao-Li Huang ◽  
Shi-Jia Ma ◽  
Shan-Yu Qin
Keyword(s):  
Th17 Cells ◽  
Malignant Ascites ◽  
Th9 Cells

scholarly journals The role of Th17 lymphocytes in pathogenesis of autoimmune arthritides

2014 ◽  
Vol 124 (1) ◽  
pp. 55-58
Author(s):  
Katarzyna Pogoda ◽  
Maria Pyszniak ◽  
Magdalena Bańka ◽  
Beata Rybojad ◽  
Jacek Tabarkiewicz
Keyword(s):  
Rheumatoid Arthritis ◽  
Juvenile Idiopathic Arthritis ◽  
Autoimmune Diseases ◽  
Inflammatory Disease ◽  
Th17 Cells ◽  
Th17 Lymphocytes ◽  
Inflammatory Phenotype ◽  
Long Time ◽  
Adults And Children

Abstract Th17 cells are newly described population of lymphoctyes, that recruits neutrophils to the site of inflammation and activate inflammatory phenotype of various tissues. They also play a pivotal role in autoimmune diseases and cancers. These cells secrete mainly different isoforms of IL-17, but also IL-21 and IL-22. Rheumatoid arthritis and juvenile idiopathic arthritis are the most common autoimmune joints’ inflammatory disease, affecting respectively adults and children. For a long time the immunopathogenesis of autoimmune diseases has been associated with Th1 lymphocytes. This hypothesis has changed after the discovery of Th17 cells, which are thought to be key mediators of autoimmune arthritides

Abstract TP50: Functional Recovery In Stroke: Performance On Verbal Fluency Task

Stroke ◽  
2013 ◽  
Vol 44 (suppl_1) ◽  
Author(s):  
VEENA A NAIR ◽  
CHRISTIAN LA ◽  
TANVI NADKARNI ◽  
PETER REITER ◽  
MARCUS CHACON ◽  
...  
Keyword(s):  
Acute Stroke ◽  
Verbal Fluency ◽  
Acute Stage ◽  
Stroke Onset ◽  
Healthy Controls ◽  
Significant Group ◽  
Verbal Fluency Task ◽  
Acute Patients ◽  
Fluency Task ◽  
Over Time

BACKGROUND: The objective of this study is to investigate the brain activation patterns and relationship with verbal fluency performance in stroke recovery. METHODS: Patients with ischemic stroke (N=19, mean age =64, 7F) and 17 healthy age-matched controls, participated in the study. Measures on a verbal fluency task were collected outside the scanner. Functional MR images were collected as subjects performed the same task(3T GE scanner). Task included alternating 20 second blocks of rest and word retrieval given a letter. Results from 19 acute patients(< 7 days from stroke onset - V1), of which 9 were also tested in the sub-acute stage(between 7 days and 6 months from stroke onset - V2), are reported here. RESULTS: Acute patients showed significantly greater activation in several regions, including the right middle and inferior frontal gyrus, and de-activations in regions including left middle temporal and frontal gyri(p<.05, corrected for multiple comparisons). Beta values representing the intensity of BOLD signal were extracted from these significant activation clusters. There were significant differences in beta values in acute(p<.001 corrected) and sub-acute(p<.01 uncorrected) stages compared with healthy controls(Figure). Pearson r correlations computed between the beta values and normed verbal fluency scores did not show significant group difference in correlation between these measures. CONCLUSIONS: Results suggest increased activation in acute stroke in right hemisphere language regions; healthy controls conversely show less activation in these regions. Additionally, activity in brain areas significantly correlated with behavior. Activation pattern in acute stroke however changes over time with patients in the sub-acute stage showing pattern similar to healthy controls. This is consistent with studies suggesting that activations in the acute stage tend to normalize over time likely due to areas prior to the stroke re-gaining function.

scholarly journals The Role of IL-17 and Related Cytokines in Inflammatory Autoimmune Diseases

2017 ◽  
Vol 2017 ◽  
pp. 1-11 ◽  
Author(s):  
Taku Kuwabara ◽  
Fumio Ishikawa ◽  
Motonari Kondo ◽  
Terutaka Kakiuchi
Keyword(s):  
T Cells ◽  
Autoimmune Diseases ◽  
Chronic Inflammation ◽  
Th17 Cells ◽  
Lymphoid Cells ◽  
Interleukin 17 ◽  
Human Rheumatoid Arthritis ◽  
Functional Understanding ◽  
Bacteria And Fungi

Interleukin-17 (IL-17) induces the production of granulocyte colony-stimulating factor (G-CSF) and chemokines such as CXCL1 and CXCL2 and is a cytokine that acts as an inflammation mediator. During infection, IL-17 is needed to eliminate extracellular bacteria and fungi, by inducing antimicrobial peptides such as defensin. This cytokine also plays an important role in chronic inflammation that occurs during the pathogenesis of autoimmune diseases and allergies such as human rheumatoid arthritis (RA) for which a mouse model of collagen-induced arthritis (CIA) is available. In autoimmune diseases such as RA and multiple sclerosis (MS), IL-17 is produced by helper T (Th) cells that are stimulated by IL-1βand IL-6 derived from phagocytes such as macrophages and from tissue cells. IL-17 contributes to various lesions that are produced by Th17 cells, one subset of helper T cells, and byγδT cells and innate lymphoid cells. It strongly contributes to autoimmune diseases that are accompanied by chronic inflammation. Thus, a functional understanding of Th17 cells is extremely important. In this review, we highlight the roles of cytokines that promote the development and maintenance of pathogenic Th17 cells in autoimmune diseases.

scholarly journals Airwayβ-Defensin-1 Protein Is Elevated in COPD and Severe Asthma

2015 ◽  
Vol 2015 ◽  
pp. 1-8 ◽  
Author(s):  
Katherine J. Baines ◽  
Thomas K. Wright ◽  
Jodie L. Simpson ◽  
Vanessa M. McDonald ◽  
Lisa G. Wood ◽  
...  
Keyword(s):  
Severe Asthma ◽  
Chronic Obstructive ◽  
Healthy Controls ◽  
Obstructive Pulmonary Disease ◽  
Bronchial Epithelial ◽  
Receiver Operating Characteristic Curves ◽  
Asthma Patients ◽  
Inflammatory Phenotype ◽  
Primary Bronchial Epithelial Cells

Background. Innate immune antimicrobial peptides, includingβ-defensin-1, promote the chemotaxis and activation of several immune cells. The role ofβ-defensin-1 in asthma and chronic obstructive pulmonary disease (COPD) remains unclear.Methods. Induced sputum was collected from healthy controls and individuals with asthma or COPD.β-defensin-1 protein in sputum supernatant was quantified by ELISA. Biomarker potential was examined using receiver operating characteristic curves.β-defensin-1 release from primary bronchial epithelial cells (pBECs) was investigated in culture with and without cigarette smoke extract (CSE).Results. Airwayβ-defensin-1 protein was elevated in COPD participants compared to asthma participants and healthy controls. Inflammatory phenotype had no effect onβ-defensin-1 levels in asthma or COPD.β-defensin-1 protein was significantly higher in severe asthma compared to controlled and uncontrolled asthma.β-defensin-1 protein could predict the presence of COPD from both healthy controls and asthma patients. Exposure of pBECs to CSE decreasedβ-defensin-1 production in healthy controls; however in pBECs from COPD participants the level ofβ-defensin-1 remanied unchanged.Conclusions. Elevatedβ-defensin-1 protein is a feature of COPD and severe asthma regardless of inflammatory phenotype.β-defensin-1 production is dysregulated in the epithelium of patients with COPD and may be an effective biomarker and potential therapeutic target.

scholarly journals Effect of Crosstalk Between Th17 and Th9 Cells on the Activation of Dermal Vascular Smooth Muscle Cells in Systemic Sclerosis and Regulation of Tanshinone IIA

2020 ◽  
Author(s):  
mengguo liu ◽  
ming li ◽  
wenwen fu
Keyword(s):  
Flow Cytometry ◽  
T Cells ◽  
Smooth Muscle ◽  
Systemic Sclerosis ◽  
Vascular Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Vascular Smooth Muscle Cells ◽  
Th17 Cells ◽  
Tanshinone Iia ◽  
Th9 Cells

Abstract Background: To evaluate the effect of T helper 17 (Th17) cells and Th9 cells on the activation of dermal vascular smooth muscle cells (DVSMCs) in systemic sclerosis (SSc) and regulation of tanshinone IIA. Methods: The expression of interleukin 17 receptor (IL-17R) and interleukin 9 receptor (IL-9R) in the skin of SSc patients was assessed by immunofluorescence. The expression of IL-9 and IL-9R mRNA in peripheral blood mononuclear cells (PBMCs) of SSc patients were detected by quantitative real-time polymerase chain reaction (qRT-PCR). The proportion of Th9 cells in PBMCs of SSc patients was sorted by flow cytometry. The effect of IL-9 on the differentiation of Th17 and IL-17 on that of Th9 was detected by flow cytometry. The proportion of Th9 and Th17 cells in SSc patients was detected by flow cytometry. The level of collagen I, III, α-SMA, IL-9R, IL-17R, JNK, P38, and ERK were analyzed using Western blot (WB).Results: Th9 cells were highly expressed in SSc. IL-9 stimulated the differentiation of immature T cells into Th17 cells. IL-17 induced the differentiation of immature T cells into Th9 cells. Tanshinone IIA inhibited the differentiation of immature T lymphocytes into Th17 and Th9. WB showed that the combined action of IL-17 and IL-9 upregulated the inflammation and proliferation of DVSMCs. Anti-IL17, anti-IL9, and tanshinone IIA inhibited the functional activation of DVSMCs.Conclusions: The current results suggested that Th17 and Th9 cells induced the activation of DVSMCs in SSc through crosstalk in vitro, and tanshinone IIA inhibited the process.

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