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.

Abstract 3598: Critical Role of Th17-CD4 + T cells in Angiogenic Response to Hindlimb Ischemia in Mice

Circulation ◽  
2008 ◽  
Vol 118 (suppl_18) ◽  
Author(s):  
Takeki Hata ◽  
Masafumi Takahashi ◽  
Masanori Kawaguchi ◽  
Yuichiro Kashima ◽  
Yuji Shiba ◽  
...  
Keyword(s):  
T Cells ◽  
Blood Flow ◽  
Th17 Cells ◽  
Critical Role ◽  
Interleukin 17 ◽  
Hindlimb Ischemia ◽  
Capillary Formation ◽  
Angiogenic Response ◽  
Flow Perfusion

Background: Accumulating evidence indicates that CD4 + T cells contribute to the development of collateral vesssels in ischemic tissue; however, little is known about the responsible subset of CD4 + T cells in the induction of angiogenesis. Th17 cells are recently identified as a new subset of CD4 + T cells and have been associated with the pathogenesis of certain autoimmune diseases. Th17 cells specifically secrete interleukin-17 (IL-17) and regulate various biological functions. The purpose of this study is to investigate the role of CD4 + T and Th17 cells in angiogenic response to hindlimb ischemia. Methods and Results: Unilateral hindlimb ischemia was produced in wild-type (WT: C57BL/6, 8- to 10-week-old) mice treated with or without a neutralizing antibody against CD4. Blood flow perfusion and capillary formation were assessed by using a laser Doppler perfusion imaging (LDPI) and CD31 immunostaining, respectively. Well-developed collateral vessels and capillary formation were observed in WT mice in response to hindlimb ischemia. Treatment with a neutralizing anti-CD4 antibody resulted in almost complete CD4 + T cell depletion (flow cytometry analysis, control: 45.4% vs. antibody: 1.0%) and a significant decrease in angiogenesis after the induction of hindlimb ischemia (LDPI, 21 days, control: 0.61 ± 0.1 vs. antibody: 0.41 ± 0.1, p<0.05). IL-17-deficient (IL-17 −/− ) mice also showed a significant reduction of blood flow perfusion, compared with WT mice (LDPI, day 14: 0.56 ± 0.3 vs. 0.31 ± 0.2, p<0.05; day 21: 0.66 ± 0.3 vs. 0.37 ± 0.3, p=0.05). IL-17 −/− mice had severe ischemic damage of the limb and resulted in a 25% incidence of autoamputation by day 21 (no limb loss in WT mice). Furthermore, capillary formation was also decreased significantly in IL-17 −/− mice (692.9 ± 165.6/mm 2 vs. 1223.3 ± 267.3/mm 2 , p<0.01). Conclusion : These findings demonstrate that Th17 cells, a new subset of CD4 + T cells, contribute to the angiogenic response to hindlimb ischemia and provide new insights into the mechanism by which T cells promote collateral development and angiogenesis.

scholarly journals AB0020 CORRELATION BETWEEN SERUM AND SYNOVIAL CONCENTRATION OF IL-17A AND MIRNA EXPRESSION IN RHEUMATOID ARTHRITIS PATIENTS

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 1313.2-1313
Author(s):  
R. Shumnalieva ◽  
D. Kachakova ◽  
T. Velikova ◽  
R. Kaneva ◽  
Z. Kolarov ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
T Cells ◽  
Roc Curve ◽  
Th17 Cells ◽  
Curve Analysis ◽  
Interleukin 17 ◽  
Roc Curve Analysis ◽  
Autoimmune Reaction ◽  
Local Levels

Background:Interleukin 17 (IL-17) is a proinflammatory cytokine, which overproduction promotes the autoimmune reaction in rheumatoid arthritis (RA). Posttranscriptional regulation of IL-17 by specific microRNAs (miRNAs) is of great interest in the recent years. 146a was associated with IL-17 expression in IL-17 producing T-cells in the synovium when miR-155 enhanced Treg and Th17 cells differentiation and IL-17A production by directly targeting the suppressor of cytokine signaling (SOCS) 1 [1, 2]. It has been shown that IL-17 production in lymphocytes or its function could be regulated by miR-223 by targeting Roquin ubiquitin ligase or its receptors [3].Objectives:To examine a possible correlation between systemic and local concentrations of IL-17A and systemic and local miR-146a, miR-155 and miR-223 expression in RA patients.Methods:Expression levels of three miRNAs were determined in matched peripheral blood (PB) and synovial fluid (SF) samples of RA patients by relative quantitation method 2-ΔΔCt. As reference control for normalization RNU6B gene was used. Concentrations of IL-17A were compared between matched serum and SF samples from 20 RA patients by Human IL-17A ELISA kit (Gene probe, Diaclone, France). Healthy donors were used as controls.Results:miR-146a, miR-155 and miR-223 showed overexpression in RA SF when compared to HCs SF (in 70.83%, p=0.007; in 79.17%, p=1.63x10-4and in 79.17%, p=1.64x10-3, respectively). The ROC curve analysis showed diagnostic accuracy for miR-146a in SF with AUC=0.769, p=0.006, AUC for SF miR-155 was 0.858, p=2.3x10-4and AUC for SF miR-223 was 0.841 p=4.6x10-4. SF levels of miR-146a and miR-155 were overexpressed in 52.17% and in 76.09% of the RA patients compared to its systemic levels. SF miR-223 was underexpressed in 58.7% of the patients compared to its systemic levels. Levels of IL-17A were higher in RA SF compared to serum (8.645 pg/ml versus 0.315 pg/ml, p=0.012). ROC curve analysis for SF IL-17A showed area under the curve (AUC) = 0.885, p<0.000.Conclusion:The difference between the systemic and local concentration of IL-17A and miRNAs expression shows that the inflammatory disease process leads to their altered expression with a possible role of these molecules in the disease pathogenesis. The higher local levels of miR-155, miR-146 and IL-17A confirm the data about the possible role of these miRNAs in regulating IL-17A production. The opposite changes of IL-17A and miR-223 systemic and local levels confirm the data about the possible role of miR-223 in regulating IL-17 function. Further analysis with larger sets is needed to confirm these results.References:[1]Niimoto T, Nakasa T, Ishikawa M, Okuhara A, Izumi B, Deie M, et al. MicroRNA-146a expresses in interleukin-17 producing T cells in rheumatoid arthritis patients. BMC Musculoskelet Disord. 2010; 11:209.[2]Yao R, Ma YL, Liang W, Li HH, Ma ZJ, Yu X. et al. MicroRNA-155 modulates Treg and Th17 cells differentiation and Th17 cell function by targeting SOCS1. PLoS ONE 2012; 7(10):e46082.[3]Schaefer J, Nakra N, Montufar-Solis D, Vigneswaran N, Klein J. Role for miR-223 and Roquin in IL-10 mediated regulation of IL-17. J Immunol. 2013; 190 (1 Supplement) 171.9.Acknowledgments:The study was supported by Grant 14-D/2012, Grant 60/2013 and Grant 61/2015 from Medical University-Sofia, BulgariaDisclosure of Interests:None declared

Calcium Signaling in T Cells and Chronic Inflammatory Disorders of the Oral Cavity

2021 ◽  
pp. 002203452199065
Author(s):  
S. Hasiakos ◽  
Y. Gwack ◽  
M. Kang ◽  
I. Nishimura
Keyword(s):  
T Cells ◽  
T Cell ◽  
Oral Cavity ◽  
Calcium Signaling ◽  
Signaling Pathways ◽  
Chronic Inflammation ◽  
Th17 Cells ◽  
Inflammatory Diseases ◽  
Chronic Inflammatory Diseases

Acute immune responses to microbial insults in the oral cavity often progress to chronic inflammatory diseases such as periodontitis and apical periodontitis. Chronic oral inflammation causes destruction of the periodontium, potentially leading to loss of the dentition. Previous investigations have demonstrated that the composition of oral immune cells, rather than the overall extent of cellular infiltration, determines the pathological development of chronic inflammation. The role of T lymphocyte populations, including Th1, Th2, Th17, and Treg cells, has been extensively described. Studies now propose pathogenic Th17 cells as a distinct subset, uniquely classifiable from traditional Th17 populations. In situ differentiation of pathogenic Th17 cells has been verified as a source of destructive inflammation, which critically drives pathogenesis in chronic inflammatory diseases such as diabetes, rheumatoid arthritis, and inflammatory bowel disease. Pathogenic Th17 cells resemble a Th1 penotype and produce not only interleukin 17 (IL-17) but also γ-interferon (IFN-γ) and granulocyte-macrophage colony-stimulating factor (GM-CSF). The proinflammatory cytokine-specific mechanisms known to induce IL-17 expression in Th17 cells are well characterized; however, differentiation mechanisms that lead to pathogenic Th17 cells are less understood. Recently, Ca2+ signaling through Ca2+ release-activated Ca2+ channels (CRAC) in T cells has been uncovered as a major signaling axis involved in the regulation of T-cell-mediated chronic inflammation. In particular, pathogenic Th17 cell–mediated immunological diseases appear to be effectively targeted via such Ca2+ signaling pathways. Pathogenic plasticity of Th17 cells has been extensively illustrated in autoimmune and chronic inflammatory diseases. Although their specific causal relationship to oral infection-induced chronic inflammatory diseases is not fully established, pathogenic Th17 cells may be involved in the underlining mechanism. This review highlights the current understanding of T-cell phenotype regulation, calcium signaling pathways in this event, and the potential role of pathogenic Th17 cells in chronic inflammatory disorders of the oral cavity.

scholarly journals Th17 immune responses contribute to the pathophysiology of aplastic anemia

Blood ◽  
2010 ◽  
Vol 116 (20) ◽  
pp. 4175-4184 ◽  
Author(s):  
Regis Peffault de Latour ◽  
Valeria Visconte ◽  
Tomoiku Takaku ◽  
Colin Wu ◽  
Andrew J. Erie ◽  
...  
Keyword(s):  
T Cells ◽  
Lymph Node ◽  
Immune Responses ◽  
Aplastic Anemia ◽  
Th17 Cells ◽  
Mononuclear Cells ◽  
Early Stage ◽  
Treg Cells ◽  
Interleukin 17

AbstractT helper type 17 (Th17) cells have been characterized based on production of interleukin-17 (IL-17) and association with autoimmune diseases. We studied the role of Th17 cells in aplastic anemia (AA) by isolating Th17 cells from patients blood (n = 41) and bone marrow (BM) mononuclear cells (n = 7). The frequency and total number of CD3+CD4+IL-17–producing T cells were increased in AA patients at presentation compared with healthy controls (P = .0007 and .02, respectively) and correlated with disease activity. There was an inverse relationship between the numbers of Th17 cells and CD4+CD25highFoxP3+ regulatory T cells (Tregs) in the blood of AA patients. Concomitant with the classical Th1 response, we detected the presence of CD4+ and CD8+ IL-17-producing T cells in a mouse model of lymph node infusion–induced BM failure. Although anti–IL-17 treatment did not abrogate BM failure, early treatment with the anti–IL-17 antibody reduced the severity of BM failure with significantly higher platelet (P < .01) and total BM cell (P < .05) counts at day 10. Recipients that received anti-IL-17 treatment had significantly fewer Th1 cells (P < .01) and more Treg cells (P < .05) at day 10 after lymph node infusion. Th17 immune responses contribute to AA pathophysiology, especially at the early stage during disease progression.

scholarly journals Adaptive Immunity: The Role of Toll-Like Receptors

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Yamaguchi R ◽  
◽  
Sakamoto A ◽  
Yamaguchi R ◽  
Haraguchi M ◽  
...  
Keyword(s):  
Immune Response ◽  
T Cells ◽  
Autoimmune Diseases ◽  
Adaptive Immunity ◽  
Th17 Cells ◽  
Adaptive Immune Response ◽  
Toll Like Receptors ◽  
Adaptive Immune ◽  
Interleukin 23

The central mediators of the adaptive immune response are T cells. The clonal expansion of T cells required for adaptive immunity results from the innate immune response, which is triggered by the stimulation of Toll-Like Receptors (TLRs). The adaptive immune response can cause autoimmune diseases, and Th17 cells are known to contribute to several autoimmune diseases. Pathogenic Th17 cells are induced by Interleukin 23 (IL-23) and IL-1Β. Resiquimod (a TLR7/8 agonist) significantly enhances IL-23 production by human macrophages, and lipopolysaccharide (a TLR4 agonist) slightly enhances it. Interestingly, IL-23 levels are significantly attenuated after sequential stimulation with lipopolysaccharide and resiquimod, indicating cross-talk between the TLR4 and TLR7/8 signaling pathways. In this review, we discuss the pivotal role of TLRs in triggering innate immunity and inducing adaptive immunity, leading to autoimmune diseases.

The role of D2-like dopaminergic receptor in dopamine-mediated modulation of Th17-cells in multiple sclerosis

2021 ◽  
Vol 19 ◽  
Author(s):  
Mikhail Melnikov ◽  
Anastasiya Sviridova ◽  
Vladimir Rogovskii ◽  
Vladimir Kudrin ◽  
Vladimir Murugin ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
T Cells ◽  
Healthy Subjects ◽  
Th17 Cells ◽  
Cell Activity ◽  
Interleukin 17 ◽  
Dopaminergic Receptor ◽  
Gm Csf ◽  
Ifn Γ

: Dopamine is a direct mediator of neuroimmune interaction and may play a significant role in multiple sclerosis (MS) pathogenesis by modulating immune cell activity and cytokine production. We studied the effects of dopamine on Th17-cells function in 34 patients with relapsing-remitting MS and 23 healthy subjects. Production of interleukin-17 (IL-17), interferon-γ (IFN-γ), granulocyte-colony stimulating factor (GM-CSF), and IL-21 by CD4+ T-cells as well as dopamine were comparable between the groups. Dopamine suppressed IL-17, IFN-γ, GM-CSF, and IL-21 production by stimulated СD4+ T-cells in both groups. Blockade of D1-like dopaminergic receptor with a specific antagonist SCH23390 did not affect dopamine-mediated cytokine suppression. In contrast, blockade of D2-like dopaminergic receptor by sulpiride decreased dopamine's inhibitory effect on IL-17 secretion in both groups and GM-CSF and IL-21 production in MS patients. Blockade of D1-like dopaminergic receptor directly inhibited IL-17, IFN-γ, GM-CSF in both groups and IL-21 production in healthy subjects, while blockade of D2-like dopaminergic receptor had no effect on cytokine secretion. Finally, activation of D2-like dopaminergic receptor with a specific agonist quinpirole decreased IL-17, IFN-γ, and GM-CSF production in both groups. These data suggest an inhibitory role of dopamine on Th17-cells in MS, which could be mediated by the activation of D2-like dopaminergic receptor.

scholarly journals Interleukin-12 Is the Optimum Cytokine To Expand Human Th17 Cells In Vitro

2009 ◽  
Vol 16 (6) ◽  
pp. 798-805 ◽  
Author(s):  
Soad Nady ◽  
James Ignatz-Hoover ◽  
Mohamed T. Shata
Keyword(s):  
T Cells ◽  
Peripheral Blood ◽  
Th17 Cells ◽  
Interleukin 12 ◽  
Interleukin 17 ◽  
Functional Evaluation ◽  
Optimum Conditions ◽  
T Helper ◽  
Ifn Γ

ABSTRACT Recently, a new lineage of CD4+ T cells in humans and in mice has been reported. This T helper cell secretes interleukin-17 (IL-17) and has been defined as T helper 17 (Th17). Th17 cells express the IL-23 receptor (IL-23R) and play an important pathogenic role in different inflammatory conditions. In this study, our aim was to characterize the optimum conditions for isolation and propagation of human peripheral blood Th17 cells in vitro and the optimum conditions for isolation of Th17 clones. To isolate Th17 cells, two steps were taken. Initially, we negatively isolated CD4+ T cells from peripheral blood mononuclear cells of a normal human blood donor. Then, we isolated the IL-23R+ cells from the CD4+ T cells. Functional studies revealed that CD4+ IL-23R+ cells could be stimulated ex vivo with anti-CD3/CD28 to secrete both IL-17 and gamma interferon (IFN-γ). Furthermore, we expanded the CD4+ IL-23R+ cells for 1 week in the presence of anti-CD3/CD28, irradiated autologous feeder cells, and different cytokines. Our data indicate that cytokine treatment increased the number of propagated cells 14- to 99-fold. Functional evaluation of the expanded number of CD4+ IL-23R+ cells in the presence of different cytokines with anti-CD3/CD28 revealed that all cytokines used (IL-2, IL-7, IL-12, IL-15, and IL-23) increased the amount of IFN-γ secreted by IL-23R+ CD4+ cells at different levels. Our results indicate that IL-7 plus IL-12 was the optimum combination of cytokines for the expansion of IL-23R+ CD4+ cells and the secretion of IFN-γ, while IL-12 preferentially stimulated these cells to secrete predominately IL-17.

scholarly journals The role of donor‐unrestricted T‐cells, innate lymphoid cells, and NK cells in anti‐mycobacterial immunity

2021 ◽  
Author(s):  
Paula Ruibal ◽  
Linda Voogd ◽  
Simone A. Joosten ◽  
Tom H. M. Ottenhoff
Keyword(s):  
T Cells ◽  
Nk Cells ◽  
Innate Lymphoid Cells ◽  
Lymphoid Cells

PL1-2. The role of inflammasome processed cytokines in driving Th17 cells and IL-17 producing γδ T cells in infection and autoimmunity

Cytokine ◽  
2011 ◽  
Vol 56 (1) ◽  
pp. 3
Author(s):  
Kingston H.G. Mills ◽  
Aisling Dunne ◽  
Lara Dungan ◽  
Jean Fletcher ◽  
Sarah Higgins ◽  
...  
Keyword(s):  
T Cells ◽  
Th17 Cells ◽  
Γδ T Cells

scholarly journals Pivotal Roles of T-Helper 17-Related Cytokines, IL-17, IL-22, and IL-23, in Inflammatory Diseases

2013 ◽  
Vol 2013 ◽  
pp. 1-13 ◽  
Author(s):  
Ning Qu ◽  
Mingli Xu ◽  
Izuru Mizoguchi ◽  
Jun-ichi Furusawa ◽  
Kotaro Kaneko ◽  
...  
Keyword(s):  
Th17 Cell ◽  
Th17 Cells ◽  
Functional Role ◽  
Inflammatory Diseases ◽  
Interleukin 17 ◽  
T Helper ◽  
T Helper 17 ◽  
Autoimmune Encephalomyelitis ◽  
Experimental Autoimmune

T-helper 17 (Th17) cells are characterized by producing interleukin-17 (IL-17, also called IL-17A), IL-17F, IL-21, and IL-22 and potentially TNF-α and IL-6 upon certain stimulation. IL-23, which promotes Th17 cell development, as well as IL-17 and IL-22 produced by the Th17 cells plays essential roles in various inflammatory diseases, such as experimental autoimmune encephalomyelitis, rheumatoid arthritis, colitis, and Concanavalin A-induced hepatitis. In this review, we summarize the characteristics of the functional role of Th17 cells, with particular focus on the Th17 cell-related cytokines such as IL-17, IL-22, and IL-23, in mouse models and human inflammatory diseases.

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