scholarly journals Role of IL-17 and Th17 Cells in Liver Diseases

2011 ◽  
Vol 2011 ◽  
pp. 1-12 ◽  
Author(s):  
Linda Hammerich ◽  
Felix Heymann ◽  
Frank Tacke
Keyword(s):  
Chemokine Receptors ◽  
Liver Diseases ◽  
Th17 Cells ◽  
Hepatic Inflammation ◽  
T Helper ◽  
Disease Etiology ◽  
Cell Recruitment ◽  
Cell Responses ◽  
Injured Liver

Unbalanced Th1/Th2 T-cell responses in the liver are a characteristic of hepatic inflammation and subsequent liver fibrosis. The recently discovered Th17 cells, a subtype of CD4+T-helper cells mainly producing IL-17 and IL-22, have initially been linked to host defense against infections and to autoimmunity. Their preferred differentiation upon TGFβand IL-6, two cytokines abundantly present in injured liver, makes a contribution of Th17 cells to hepatic inflammation very likely. Indeed, initial studies in humans revealed activated Th17 cells and Th17-related cytokines in various liver diseases. However, functional experiments in mouse models are not fully conclusive at present, and the pathogenic contribution of Th17 cells to liver inflammation might vary upon the disease etiology, for example, between infectious and autoimmune disorders. Understanding the chemokines and chemokine receptors promoting hepatic Th17 cell recruitment (possibly CCR6 or CCR4) might reveal new therapeutic targets interfering with Th17 migration or differentiation in liver disease.

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 Dendritic cells mediate the induction of polyfunctional human IL17-producing cells (Th17-1 cells) enriched in the bone marrow of patients with myeloma

Blood ◽  
2008 ◽  
Vol 112 (7) ◽  
pp. 2878-2885 ◽  
Author(s):  
Kavita M. Dhodapkar ◽  
Scott Barbuto ◽  
Phillip Matthews ◽  
Anjli Kukreja ◽  
Amitabha Mazumder ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Dendritic Cells ◽  
Th17 Cells ◽  
T Helper ◽  
Tumor Bed ◽  
Distinct Lineage ◽  
Human Dendritic Cells ◽  
Antigen Presenting ◽  
Dc Maturation

Abstract IL17-producing (Th17) cells are a distinct lineage of T helper cells that regulate immunity and inflammation. The role of antigen-presenting cells in the induction of Th17 cells in humans remains to be fully defined. Here, we show that human dendritic cells (DCs) are efficient inducers of Th17 cells in culture, including antigen-specific Th17 cells. Although most freshly isolated circulating human Th17 cells secrete IL17 alone or with IL2, those induced by DCs are polyfunctional and coexpress IL17 and IFNγ (Th17-1 cells). The capacity of DCs to expand Th17-1 cells is enhanced upon DC maturation, and mature DCs are superior to monocytes for the expansion of autologous Th17 cells. In myeloma, where tumors are infiltrated by DCs, Th17 cells are enriched in the bone marrow relative to circulation. Bone marrow from patients with myeloma contains a higher proportion of Th17-1 cells compared with the marrow in preneoplastic gammopathy (monoclonal gammopathy of undetermined significance [MGUS]). Uptake of apoptotic but not necrotic myeloma tumor cells by DCs leads to enhanced induction of Th17-1 cells. These data demonstrate the capacity of DCs to induce expansion of polyfunctional IL17-producing T cells in humans, and suggest a role for DCs in the enrichment of Th17-1 cells in the tumor bed.

scholarly journals Pathogen-Associated Molecular Patterns Induced Crosstalk between Dendritic Cells, T Helper Cells, and Natural Killer Helper Cells Can Improve Dendritic Cell Vaccination

2016 ◽  
Vol 2016 ◽  
pp. 1-12 ◽  
Author(s):  
Tammy Oth ◽  
Joris Vanderlocht ◽  
Catharina H. M. J. Van Elssen ◽  
Gerard M. J. Bos ◽  
Wilfred T. V. Germeraad
Keyword(s):  
Dendritic Cells ◽  
Nk Cells ◽  
Natural Killer ◽  
Specific Pattern ◽  
Dendritic Cell Vaccination ◽  
T Helper ◽  
Cell Responses ◽  
Helper Cells ◽  
Molecular Patterns

A coordinated cellular interplay is of crucial importance in both host defense against pathogens and malignantly transformed cells. The various interactions of Dendritic Cells (DC), Natural Killer (NK) cells, and T helper (Th) cells can be influenced by a variety of pathogen-associated molecular patterns (PAMPs) and will lead to enhanced CD8+effector T cell responses. Specific Pattern Recognition Receptor (PRR) triggering during maturation enables DC to enhance Th1 as well as NK helper cell responses. This effect is correlated with the amount of IL-12p70 released by DC. Activated NK cells are able to amplify the proinflammatory cytokine profile of DC via the release of IFN-γ. The knowledge on how PAMP recognition can modulate the DC is of importance for the design and definition of appropriate therapeutic cancer vaccines. In this review we will discuss the potential role of specific PAMP-matured DC in optimizing therapeutic DC-based vaccines, as some of these DC are efficiently activating Th1, NK cells, and cytotoxic T cells. Moreover, to optimize these vaccines, also the inhibitory effects of tumor-derived suppressive factors, for example, on the NK-DC crosstalk, should be taken into account. Finally, the suppressive role of the tumor microenvironment in vaccination efficacy and some proposals to overcome this by using combination therapies will be described.

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.

scholarly journals Pro-Tumor and Anti-Tumor Functions of IL-17 and of TH17 Cells in Tumor Microenvironment

2016 ◽  
Vol 43 (2) ◽  
pp. 68-79 ◽  
Author(s):  
M. Gulubova ◽  
J. Ananiev ◽  
M. Ignatova ◽  
K. Halacheva
Keyword(s):  
T Cells ◽  
Cell Differentiation ◽  
Tumor Microenvironment ◽  
Th17 Cells ◽  
T Helper ◽  
Main Attention ◽  
Tumor Microenvironments ◽  
Th17 Cell Differentiation ◽  
Regulatory Functions

Summary The current review reveals the seven subclasses of CD4+ T helper cells, i.e. Th1, Th2, Th9, Th17, Th22, regulatory T cells and Tfh, the cytokines produced by them and their role in tumor microenvironment. Main attention was paid to IL-17 and Th17 cells. IL-17-producing cells were described, among which were Treg17 cells and Tc17 cells. The transcription factors, engaged in the activation of Th17 cell differentiation were reviewed. It was shown that Th17 cells might possess regulatory functions in tumor microenvironments that directs toward immunosuppression. The reciprocity between Treg and Th17 cells is realized when the production of a large amount of TGF-β in tumors causes Treg cell differentiation, and the addition of IL-6 shifts the differentiation of naïve T cells to Th17 cells. The main pro-tumor role of IL-17 is the promotion of tumor angiogenesis through stimulation of fibroblasts and endothelial cells. The antitumor functions of IL-17 are associated with enhancement of cytotoxic activity of tumor specific CTL cells and with angiogenesis that provide channels through which immune cells might invade tumor and promote antitumor immunity.

scholarly journals Aberrant T Helper 17 Cells and Related Cytokines in Bone Marrow Microenvironment of Patients with Acute Myeloid Leukemia

2013 ◽  
Vol 2013 ◽  
pp. 1-10 ◽  
Author(s):  
Tian Tian ◽  
Shuang Yu ◽  
Min Wang ◽  
Cunzhong Yuan ◽  
Hua Zhang ◽  
...  
Keyword(s):  
Th17 Cells ◽  
Myeloid Leukemia ◽  
Th1 Cells ◽  
T Helper ◽  
Significant Elevation ◽  
T Helper 17 ◽  
T Helper 17 Cells ◽  
Acute Myeloid ◽  
Refractory Aml

In this study, we mainly investigate the role of Th17 cells, Th1 cells, and their related cytokines in the pathophysiology of AML. BM and PB were extracted from ND, CR, and relapsed-refractory AML patients and controls. Th subsets frequencies were examined by flow cytometry. BM plasma Th-associated cytokines levels were determined by ELISA. The frequencies of Th17 and Th1, and IFN-γor TGF-βconcentrations were significantly decreased in ND compared with CR patients or controls. Th17 percentage was significantly lower in BM than in PB for ND patients but was higher in BM for CR patients. However, in CR or relapsed-refractory patients, Th1 percentage in BM was higher than that in PB. Moreover, BM IL-17A level showed a decreased trend in ND patients. A significant elevation of plasma IL-6 level was found in ND compared with CR patients or controls. IL-17A showed the positive correlation with IL-6 concentration. And Th17 cells frequencies and TGF-β1 concentration were increased in BM from AML patients achieving CR after chemotherapy. Moreover, a significant decrease of BM plasma TGF-β1 level was found in M3 patients compared with the other subtypes. Our findings suggest that Th17 and related cytokines may be implicated in AML pathogenesis.

T helper cells in depression: central role of Th17 cells

2021 ◽  
pp. 1-21
Author(s):  
Raghumoy Ghosh ◽  
Prasenjit Mitra ◽  
P. V. S. N. Kiran Kumar ◽  
Taru Goyal ◽  
Praveen Sharma
Keyword(s):  
T Helper Cells ◽  
Th17 Cells ◽  
T Helper ◽  
Helper Cells

scholarly journals Death Ligand Tumor Necrosis Factor-Related Apoptosis-Inducing Ligand Inhibits Experimental Autoimmune Thyroiditis

Endocrinology ◽  
2005 ◽  
Vol 146 (11) ◽  
pp. 4721-4726 ◽  
Author(s):  
Su He Wang ◽  
Zhengyi Cao ◽  
Julie M. Wolf ◽  
Mary Van Antwerp ◽  
James R. Baker
Keyword(s):  
Autoimmune Thyroiditis ◽  
T Helper ◽  
Mononuclear Cell Infiltration ◽  
T Helper 1 ◽  
Experimental Autoimmune Thyroiditis ◽  
Cell Responses ◽  
Control Protein ◽  
Necrosis Factor ◽  
Experimental Autoimmune

The role of TNF-related apoptosis-inducing ligand (TRAIL) in autoimmune thyroiditis is unclear. We used experimental autoimmune thyroiditis to clarify the contribution of TRAIL to the development of autoimmune thyroiditis. CBA/J mice were immunized with murine thyroglobulin, and spleen cells from these mice were subsequently injected into irradiated recipient CBA/J mice. One week later, the recipient mice were treated with recombinant TRAIL or a control protein. Compared with control animals, TRAIL-treated mice developed a milder form of the disease with a significant decrease in mononuclear cell infiltration in the thyroid and less thyroid follicular destruction. Furthermore, the number of apoptotic thyrocytes and also thyroglobulin-specific T helper-1 cell responses in TRAIL-treated mice was lower than that in the control animals. This study suggests that exogenous TRAIL suppresses the development of autoimmune thyroiditis via altering the function of cells involved in the immune response. These findings may contribute toward a novel treatment autoimmune thyroiditis.

IL-17A, IL-22, and IL-23 as Markers of Psoriasis Activity

2015 ◽  
Vol 19 (6) ◽  
pp. 555-560 ◽  
Author(s):  
Christina Fotiadou ◽  
Elizabeth Lazaridou ◽  
Eleni Sotiriou ◽  
Spiridon Gerou ◽  
Athanasios Kyrgidis ◽  
...  
Keyword(s):  
Th17 Cells ◽  
Tumor Necrosis ◽  
Serum Levels ◽  
Sensitivity Analyses ◽  
T Helper ◽  
T Helper 1 ◽  
Factor Α ◽  
Necrosis Factor ◽  
Active Disease

Introduction: T-helper 1 (Th1), Th17 cells, and their related cytokines are implicated in psoriasis pathogenesis although the contribution of each group of cytokines in psoriasis activity has not been fully clarified. Objectives: To investigate whether Th17-related cytokines are associated with psoriasis activity. Methods: The serum levels of interleukin (IL)-1β, 6, 8, 17Α, 22, 23, and tumor necrosis factor-α (TNFα) were measured with flow cytometry in 35 patients with plaque psoriasis (21 with stable and 14 with active disease) and in 20 healthy controls. Results: Interleukin-6, 8, 17A, 22, 23, and TNFα were significantly elevated in psoriasis patients compared with controls. In the sensitivity analyses, patients with active disease showed significantly increased levels of IL-17A, IL-23, and IL-22 as compared to the group of patients with stable psoriasis. Conclusions: Our study highlights a possible crucial role of IL-17A, IL-22, and IL-23 in the activity of psoriasis and the early stages of the disease.

scholarly journals NF-κB-94ins/del ATTG Genotype Contributes to the Susceptibility and Imbalanced Th17 Cells in Patients with Immune Thrombocytopenia

2018 ◽  
Vol 2018 ◽  
pp. 1-12 ◽  
Author(s):  
Jie Yu ◽  
Mingqiang Hua ◽  
Xueyun Zhao ◽  
Rui Wang ◽  
Chaoqing Zhong ◽  
...  
Keyword(s):  
Mrna Expression ◽  
Nlrp3 Inflammasome ◽  
Th17 Cells ◽  
Immune Thrombocytopenia ◽  
Dose Effect ◽  
T Helper ◽  
Expression Of Genes ◽  
Significant Difference ◽  
Significant Gene

Background. The NLRP3 inflammasome plays important roles in the pathogenesis of autoimmune diseases. However, the role of the NLRP3 inflammasome in the pathophysiology of immune thrombocytopenia (ITP) remains unclear. Methods. RT-PCR was used to examine the polymorphism and expression of genes involved in the NLRP3 inflammasome in ITP patients. T helper cells and apoptosis of PBMC from ITP patients were analyzed by flow cytometry. The antiplatelet autoantibodies in plasma were determined by modified monoclonal antibody-specific immobilization of platelet antigens (MAIPA). Results. We found that the NF-κB-94ins/del ATTG genotype contributed to the susceptibility of ITP. Furthermore, the platelet counts of ITP patients with the WW genotype or WD genotype were lower than those with the DD genotype of NF-κB-94ins/del ATTG. Compared with controls, NF-κB gene expression was significantly decreased and WW or WD genotype ITP patients displayed higher mRNA expression than DD individuals. Similarly, the mRNA expression of NLRP3 was also increased in the WW genotype. There was a significant gene dose effect of the percentage of Th17 cells for the WW, WD, and DD genotypes (WW < WD < DD) in the unstimulated group and no significant difference was found after being stimulated. The activation of the NLRP3 inflammasome could upregulate Th17 in ITP patients. Conclusion. The NF-κB-94ins/del ATTG genotype might serve as a novel biomarker and potential target for ITP.

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