scholarly journals The Role of Th17 Cells and IL-17 in Th2 Immune Responses of Allergic Conjunctivitis

2020 ◽  
Vol 2020 ◽  
pp. 1-9
Author(s):  
Xiang-Tian Meng ◽  
Yun-Yue Shi ◽  
Hong Zhang ◽  
Hong-Yan Zhou
Keyword(s):  
Immune Response ◽  
Immune Responses ◽  
Lupus Erythematosus ◽  
Th17 Cells ◽  
Allergic Conjunctivitis ◽  
Interleukin 17 ◽  
Type I ◽  
T Helper ◽  
Th2 Immune Response

Allergic conjunctivitis (AC) is a common allergic disease that is often associated with the onset of rhinitis or asthma. The incidence of AC has increased significantly in recent years possibly due to air pollution and climate warming. AC seriously affects patients’ quality of life and work efficiency. Th (T-helper) 2 immune responses and type I hypersensitivity reactions are generally considered the basis of occurrence of AC. It has been found that new subpopulations of T-helper cells, Th17 cells that produce interleukin-17 (IL-17), play an important role in the Th2-mediated pathogenesis of conjunctivitis. Studies have shown that Th17 cells are involved in a variety of immune inflammation, including psoriasis, rheumatoid arthritis, inflammatory bowel disease, systemic lupus erythematosus, and asthma. However, the role of Th17 and IL-17 in AC is unclear. This paper will focus on how T-helper 17 cells and interleukin-17 are activated in the Th2 immune response of allergic conjunctivitis and how they promote the Th2 immune response of AC.

scholarly journals T Helper Type 17 Immune Response Plays an Indispensable Role for Development of Iodine-Induced Autoimmune Thyroiditis in Nonobese Diabetic-H2h4 Mice

Endocrinology ◽  
2009 ◽  
Vol 150 (11) ◽  
pp. 5135-5142 ◽  
Author(s):  
Ichiro Horie ◽  
Norio Abiru ◽  
Yuji Nagayama ◽  
Genpei Kuriya ◽  
Ohki Saitoh ◽  
...  
Keyword(s):  
Immune Response ◽  
Autoimmune Thyroiditis ◽  
Th17 Cells ◽  
Intermediate Phenotype ◽  
Lymphocyte Infiltration ◽  
Wild Type ◽  
T Helper ◽  
Nonobese Diabetic ◽  
Th2 Immune Response ◽  
Helper Type

T helper type 1(Th1)/Th2 paradigm has been expanded by discovery of a novel effector T cell (Teff) subset, Th17 cells, which produce a proinflammatory cytokine IL-17. Th17 cells have recently been shown to play a major role in numerous autoimmune diseases that had previously been thought to be Th1-dominant diseases. We here studied the significance of Th17 cells in iodine-induced autoimmune thyroiditis in nonobese diabetic-H2h4 mice, a mouse model of Hashimoto’s thyroiditis in humans, which spontaneously develop antithyroglobulin autoantibodies and intrathyroidal lymphocyte infiltration when supplied with iodine in the drinking water. We observed increased numbers of Th1 and Th17 cells in spleen and accumulation of both types of Teff in the thyroid glands of iodine-fed wild-type mice, indicating that Th17 cells as well as Th1 cells constitute thyroid lesions. Furthermore, the incidence and severity of intrathyroidal lymphocyte infiltration, and the titers of antithyroglobulin autoantibodies were markedly reduced in iodine-treated IL-17−/− mice as compared with wild-type mice. Of interest, IL-17+/− mice showed an intermediate phenotype. Therefore, the present study, together with a previous report demonstrating the importance of Th1, not Th2, immune response for developing thyroiditis using mice deficient for interferon-γ or IL-4, clearly indicates that both Th1 and Th17 cells are critical Teff subsets for the pathogenesis of spontaneous autoimmune thyroiditis in nonobese diabetic-H2h4 mice.

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.

scholarly journals Balance between Regulatory T and Th17 Cells in Systemic Lupus Erythematosus: The Old and the New

2012 ◽  
Vol 2012 ◽  
pp. 1-5 ◽  
Author(s):  
Alessia Alunno ◽  
Elena Bartoloni ◽  
Onelia Bistoni ◽  
Giuseppe Nocentini ◽  
Simona Ronchetti ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
T Lymphocytes ◽  
Lupus Erythematosus ◽  
Th17 Cells ◽  
Current Knowledge ◽  
Treg Cells ◽  
T Helper ◽  
Systemic Lupus ◽  
Target Organs

Pathogenic mechanisms underlying the development of systemic lupus erythematosus (SLE) are very complex and not yet entirely clarified. However, the pivotal role of T lymphocytes in the induction and perpetuation of aberrant immune response is well established. Among T cells, IL-17 producing T helper (Th17) cells and regulatory T (Treg) cells represent an intriguing issue to be addressed in SLE pathogenesis, since an imbalance between the two subsets has been observed in the course of the disease. Treg cells appear to be impaired and therefore unable to counteract autoreactive T lymphocytes. Conversely, Th17 cells accumulate in target organs contributing to local IL-17 production and eventually tissue damage. In this setting, targeting Treg/Th17 balance for therapeutic purposes may represent an intriguing and useful tool for SLE treatment in the next future. In this paper, the current knowledge about Treg and Th17 cells interplay in SLE will be discussed.

Plasmacytoid Dendritic Cells (PDC) and Th17 Immune Response Contribution in Gut Acute Graft-Versus-Host-Disease (GVHD)

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 2968-2968
Author(s):  
Florent Malard ◽  
Céline Bossard ◽  
Jessy Arbez ◽  
Patrice Chevallier ◽  
Thierry Guillaume ◽  
...  
Keyword(s):  
Immune Response ◽  
Stem Cell ◽  
Autoimmune Diseases ◽  
Intestinal Mucosa ◽  
Th17 Cells ◽  
Acute Gvhd ◽  
Type I ◽  
Type I Ifn ◽  
Th17 Response

Abstract Abstract 2968 Background. Acute GVHD after allogeneic stem cell transplantation (allo-SCT) is an exaggerated immune response against alloantigens involving dysregulation of inflammatory cytokine cascades. Previous studies established an important role of Th1 cells in acute GVHD pathophysiology. However, the identification of proinflammatory Th17 cells which contribute to autoimmune diseases pathophysiology, raised the issue of the role of Th17 cells in human acute GVHD. Indeed, the contribution of Th17 cells in acute GVHD was assessed in GVHD mouse models with conflicting results. In addition, the role of the PDC subset (the professional type I IFN-secreting cells), which play an important role in triggering Th17-related cytokines and autoimmune diseases, is not yet established in the acute GVHD setting. This report investigated the role of Th17 cells and their interaction with PDC in gastrointestinal (GI) biopsies taken from patients with or without acute GVHD. Patients and Methods. Studies described in this report were performed in a single centre series of 21 patients who underwent allo-SCT for different hematological malignancies (n=19) and severe aplastic anemia (n=2). The median age of patients was 53 years (range, 16–69). The stem cell source was PBSCs in 19 cases (85%), CB in 2 cases and BM in one case. Ten patients received transplant from a matched-related donor, and 11 patients from a matched-unrelated donor. A reduced-intensity conditioning regimen was used in the majority of cases (n=19; 90%) Immunohistochemistry was performed on deparaffinized tissues sections using an indirect immunoperoxydase method. A quantitative evaluation of antigens expression was performed by counting the number of positive cells in the whole biopsy at 200 magnifications for each sample. Results. In this cohort, based on standard pathology criteria, 16 patients had a histologically proven gastrointestinal acute GVHD. In all cases, biopsies were taken before initiation of systemic corticosteroid therapy. The remaining 5 patients did not have histological signs of acute GVHD (and did not develop clinical signs of acute GVHD) and thus, were used as controls. In order to identify the Th17 cell population, biopsies were tested for expression of the CD161 and CCR6 markers, and ROR-gamma-t, the key transcription factor that orchestrates the differentiation of Th17 cells. Significantly higher numbers of ROR-gamma-t+ and CD161+ cells were counted in the intestinal mucosa of patients with acute GVHD compared with intestinal mucosa of patients without acute GVHD, mainly found in the lamina propria but also in the epithelium of altered glands (p=0.016 and p=0.009 for ROR-gamma-t and CD161 expression respectively). Given the role of PDCs in triggering Th17-related cytokines, we sought next to determine the proportion of PDCs in intestinal biopsies from these same patients. This analysis showed a significant increase of CD123+ PDCs in the intestinal mucosa of patients with acute GVHD compared with mucosa of patients without acute GVHD (p=0.017). Moreover, we observed a significant correlation between the number of CD123+ PDCs and ROR-gamma-t or CD161 expressing cells in the intestinal mucosa of acute GVHD patients, highlighting the link between PDC and Th17 cells. Conclusion. The current study shed some light on the role of Th17 cells in the context of gastro-intestinal acute GVHD. Using well-established specific markers, we show that Th17 cells infiltrate intestinal biopsies from patients with acute GVHD. In addition, Th17 infiltration was paralleled by the infiltration of PDCs, suggesting a potential new pathophysiological link between PDCs and Th17 response in the context of gastro-intestinal acute GVHD. This is consistent with studies showing that PDCs can drive the differentiation of Th17 cells. Functional analyses are currently ongoing. Although the exact mechanism that links type I IFN production to PDC-mediated Th17 responses is still unclear in acute GVHD, these data raise the prospect of future innovative approaches to optimize immunosuppression regimens for the treatment or prophylaxis of acute GVHD by targeting PDCs and the Th17 response. Disclosures: No relevant conflicts of interest to declare.

Plasmacytoid Dendritic Cells (PDC) and Th17 Immune Response Contribution in Skin Acute Graft-Versus-Host-Disease (GVHD)

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 4103-4103
Author(s):  
Florent Malard ◽  
Céline Bossard ◽  
Patrice Chevallier ◽  
Thierry Guillaume ◽  
Jacques Delaunay ◽  
...  
Keyword(s):  
Immune Response ◽  
Stem Cell ◽  
Autoimmune Diseases ◽  
Th17 Cells ◽  
Acute Gvhd ◽  
Unrelated Donor ◽  
Type I ◽  
Type I Ifn ◽  
Th17 Response

Abstract Abstract 4103 Background. Acute GVHD after allogeneic stem cell transplantation (allo-SCT) is an exaggerated immune response against alloantigens involving dysregulation of inflammatory cytokine cascades. Previous studies established an important role of Th1 cells in acute GVHD pathophysiology. However, the identification of proinflammatory Th17 cells which contribute to autoimmune diseases pathophysiology, raised the issue of the role of Th17 cells in human acute GVHD. Indeed, the contribution of Th17 cells in acute GVHD was assessed in GVHD mouse models with conflicting results. In addition, the role of the PDC subset (the professional type I IFN-secreting cells), which play an important role in triggering Th17-related cytokines and autoimmune diseases, is not yet established in the acute GVHD setting. This report investigated the role of Th17 cells and their interaction with PDC in cutaneous biopsies taken from patients with or without acute GVHD. Patients and Methods. Studies described in this report were performed in a single centre series of 38 patients who underwent allo-SCT for different hematological malignancies (n=37) and severe aplastic anemia (n=1). The median age of patients was 52 years (range, 17–70). The stem cell source was PBSCs in 27 cases (71%), CB in 6 cases and BM in 5 cases. 11 patients received transplant from a matched-related donor, and 27 patients from an unrelated donor. A reduced-intensity conditioning regimen was used in the majority of cases (n=29; 76%) Immunohistochemistry was performed on deparaffinized tissues sections using an indirect immunoperoxydase method. A quantitative evaluation of antigens expression was performed by counting the number of positive cells in the whole biopsy at 200 magnifications for each sample. Results. In this cohort, based on standard pathology criteria, 29 patients had a histologically proven skin acute GVHD. In all cases, biopsies were taken before initiation of systemic corticosteroid therapy. The remaining 9 patients did not have histological signs of acute GVHD (and did not develop clinical signs of acute GVHD) and thus, were used as controls. In order to identify the Th17 cell population, biopsies were tested for expression of the CD161 and CCR6 markers, and ROR-gamma-t, the key transcription factor that orchestrates the differentiation of Th17 cells. Significantly higher numbers of ROR-gamma-t+, CD161+ and CCR6+ cells were counted in the skin of patients with acute GVHD compared with intestinal mucosa of patients without acute GVHD, mainly found in the lamina propria but also in the epithelium of altered glands (p=0.001, p<0.0001 and p=0.01 for ROR-gamma-t, CD161 and CCR6 expression respectively).Given the role of PDCs in triggering Th17-related cytokines, we sought next to determine the proportion of PDCs in cutaneous biopsies from these same patients. This analysis showed a significant increase of BDCA2+ PDCs in the skin of patients with acute GVHD compared with skin of patients without acute GVHD (p=0.03). Moreover, we observed a strong expression of the type I IFN-inducible protein Mx1 in the skin of patients with acute GVHD compared with skin of patients without acute GVHD, reflecting the high production of type I IFN by the BDCA2+ PDCs. Conclusion. The current study shed some light on the role of Th17 cells in the context of cutaneous acute GVHD. Using well-established specific markers, we show that Th17 cells infiltrate skin biopsies from patients with acute GVHD. In addition, Th17 infiltration was paralleled by the infiltration of PDCs, suggesting a potential new pathophysiological link between PDCs and Th17 response in the context of cutaneous acute GVHD. This is consistent with studies showing that PDCs can drive the differentiation of Th17 cells. Functional analyses are currently ongoing. These data raise the prospect of future innovative approaches to optimize immunosuppression regimens for the treatment or prophylaxis of acute GVHD by targeting PDCs and the Th17 response. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Control of Giardiasis by Interleukin-17 in Humans and Mice—Are the Questions All Answered?

2015 ◽  
Vol 23 (1) ◽  
pp. 2-5 ◽  
Author(s):  
Steven M. Singer
Keyword(s):  
Immune Response ◽  
Immune Responses ◽  
Giardia Lamblia ◽  
Antigenic Variation ◽  
Interleukin 17 ◽  
Content Type ◽  
Humoral Immune ◽  
Humoral Immune Responses ◽  
Key Factor

ABSTRACTFor years, studies of the immune response toGiardia lambliainfection focused on the production of IgA by infected hosts and antigenic variation by the parasite to escape destruction by this IgA. A new study by Hanevik and colleagues (C. S. Saghaug, S. Sørnes, D. Peirasmaki, S. Svärd, N. Langeland, and K. Hanevik, Clin Vaccine Immunol 23:11–18, 2016,http://dx.doi.org/10.1128/CVI.00419-15) highlights the emerging role of interleukin-17 (IL-17) in immunity to this parasite. Along with recent studies ofGiardiainfections of animals, this work shows that IL-17 appears to be essential for the control of these infections and to be a key factor linking cellular and humoral immune responses.

scholarly journals Polymorphisms in STING affect human innate immune responses to poxviruses

2020 ◽  
Author(s):  
Richard B. Kennedy ◽  
Iana H. Haralambieva ◽  
Inna G. Ovsyannikova ◽  
Emily A. Voigt ◽  
Beth R. Larrabee ◽  
...  
Keyword(s):  
Immune Response ◽  
Molecular Modeling ◽  
Immune Responses ◽  
Genetic Variants ◽  
Innate Immune ◽  
Smallpox Vaccination ◽  
Type I ◽  
Innate Immune Responses ◽  
Dna Viruses

AbstractWe conducted a large genome-wide association study (GWAS) of the immune responses to primary smallpox vaccination in a combined cohort of > 1,600 subjects. We identified a cluster of SNPs on chromosome 5 (5q31.2) that were significantly associated (p-value: 1.3 × 10−12 – 1.5×10−36) with IFNα response to in vitro poxvirus stimulation. Examination of these SNPs led to the functional testing of rs1131769, a non-synonymous SNP in TMEM173 causing an Arg-to-His change at position 232 in the STING protein—a major regulator of innate immune responses to viral infections. Our findings demonstrate important functional differences between the two alleles, where the major allele (R232) more effectively induces IFNα secretion. Molecular modeling of both alleles identified altered ligand binding characteristics between the two variants, providing a potential mechanism underlying differences in inter-individual responses to poxvirus vaccination. Our data demonstrate that possession of the H232 variant impairs STING-mediated innate immunity to poxviruses. These results clarify prior studies evaluating functional effects of genetic variants in TMEM173 and provide novel data regarding genetic control of poxvirus immunity.Contribution to the FieldHere we report that a single nucleotide non-synonymous polymorphism in the TMEM173 gene encodes for a STING variant conferring a reduced IFN stimulated response compared to wild type. Our results suggest that, upon binding of the STING H232 variant to its ligand, activation of downstream signaling proteins is impaired, resulting in decreased production of IFNα and a weaker interferon-stimulated gene response. Molecular modeling indicates that the diminished functional activity of this variant is likely due to an altered physical structure of the STING protein. STING controls the innate, type I IFN response to double-stranded DNA and cyclic dinucleotides. Individuals with the H232 variant of STING have a much weaker innate immune response to vaccinia virus. Our data help resolve ongoing controversies regarding the role of genetic variants in STING function. Because STING plays an important role in our immune response to DNA viruses and bacteria, our results can be used to predict who will and will not respond to vaccines and treatments, and to design more effective vaccine candidates. Given the role of the STING protein in innate responses to DNA viruses and bacterial pathogens, these data may also be useful in developing novel treatment options for multiple infectious diseases.

scholarly journals Babassu aqueous extract (BAE) as an adjuvant for T helper (Th)1-dependent immune responses in mice of a Th2 immune response-prone strain

2011 ◽  
Vol 12 (1) ◽  
Author(s):  
Rosane NM Guerra ◽  
Virgínia MG Silva ◽  
Luciana S Aragão-França ◽  
Pablo R Oliveira ◽  
Rodrigo Feitosa ◽  
...  
Keyword(s):  
Immune Response ◽  
Immune Responses ◽  
Aqueous Extract ◽  
T Helper ◽  
Th2 Immune Response ◽  
Th 1

Interleukin-17 in Liver Disease Pathogenesis

2021 ◽  
Author(s):  
Na Li ◽  
Gen Yamamoto ◽  
Hiroaki Fuji ◽  
Tatiana Kisseleva
Keyword(s):  
Liver Disease ◽  
Liver Injury ◽  
Th17 Cells ◽  
Transforming Growth Factor ◽  
Critical Role ◽  
Experimental Models ◽  
Interleukin 17 ◽  
Orphan Nuclear Receptor ◽  
T Helper

AbstractInterleukin 17A (IL-17A)-producing T helper 17 (Th17) cells were identified as a subset of T helper cells that play a critical role in host defense against bacterial and fungal pathogens. Th17 cells differentiate from Th0 naïve T-cells in response to transforming growth factor β1 (TGF-β1) and IL-6, the cytokines which also drive development of liver fibrosis, require activation of transcription factor retinoic acid receptor-related orphan nuclear receptor gamma t (RORγt). IL-17A signals through the ubiquitously expressed receptor IL-17RA. Expression of IL-17RA is upregulated in patients with hepatitis B virus/hepatitis C virus (HBV/HCV) infections, nonalcoholic steatohepatitis (NASH), alcohol-associated liver disease (AALD), hepatocellular carcinoma (HCC), and experimental models of chronic toxic liver injury. The role of IL-17 signaling in the pathogenesis of NASH- and AALD-induced metabolic liver injury and HCC will be the focus of this review. The role of IL-17A–IL-17RA axis in mediation of the cross-talk between metabolically injured hepatic macrophages, hepatocytes, and fibrogenic myofibroblasts will be discussed.

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.

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