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Peng You, Ning Chen, Lin Su, Tao Peng, Guodong Chen, Yulan Liu
Transforming growth factor β1 (TGF-β1) has a crucial role in regulating the balance of type 17 T-helper cells (Th17) and T regulatory cells (Tregs) that are involved in the pathogenesis of inflammatory bowel disease, while the function of local TGF-β1 in this process has remained to be fully elucidated. The present study investigated the effects of different local TGF-β1 levels on the Treg/Th17 balance and on the dexamethasone efficacy in mice with 2,4,6-trinitrobenzenesulfonic acid (TNBS)-induced colitis...
April 2018: Experimental and Therapeutic Medicine
Takehiro Takahashi, Yoko Koga, Mie Kainoh
Psoriasis is a chronic inflammatory skin disease characterized by erythema, skin hyperplasia, scales, and keratinocyte hyperproliferation. While the cause of psoriasis is not clearly understood, a dysregulated immune system, especially activation of IL-23/IL-17 axis, has been strongly implicated in the pathogenesis of psoriasis. For example, anti-IL-23 therapy is effective in psoriasis patients, and thus IL-23 is considered as a potential therapeutic target for the treatment of psoriasis. The skin barrier provides protection of the human body against infection from external pathogens...
March 12, 2018: European Journal of Pharmacology
Ji Young Kim, Kyu Lim, Kyung Hee Kim, Jin Hyun Kim, Jin Sun Choi, Seung-Cheol Shim
N-3 polyunsaturated fatty acids (PUFA) have anti-inflammatory effects and were considered useful for the treatment of rheumatoid arthritis (RA). Recently, several studies suggested that n-3 PUFAs attenuated arthritis in animal model and human, however the mechanism is still unclear. Interleukin 17 (IL-17) is a pro-inflammatory cytokine mainly produced by T helper 17 (Th17) cells which cause tissue inflammation and bone erosion leading to joint destruction. In contrast, regulatory T (Treg) cells down-regulate various immune responses by suppression of naïve T cells...
2018: PloS One
Anh Duc Truong, Cong Thanh Hoang, Yeojin Hong, Janggeun Lee, Kyungbaek Lee, Hyun S Lillehoj, Yeong Ho Hong
The data herein is related to the research article entitled "Functional analyses of the interaction of chicken interleukin 23 subunit p19 with IL-12 subunit p40 to form the IL-23 complex" [1] where we demonstrated that the chicken interleukin (IL)-23α, IL-12p40, and IL-23 complex regulates Th1, Th17, and Treg cytokine production through heterodimer receptors as well as a homodimer receptor consisting of IL-12Rβ1 and IL-23R, and activates the JAK/STAT signaling pathways. Here, we evaluated the effects of the recombinant chicken IL-23α, IL-12p40, and IL-23 complex protein on cell proliferation and nitric oxide (NO) production in chicken macrophage (HD11) and CU91 T cell lines...
February 2018: Data in Brief
Charlie Bridgewood, Gareth W Fearnley, Anna Berekmeri, Philip Laws, Tom Macleod, Sreenivasan Ponnambalam, Martin Stacey, Anne Graham, Miriam Wittmann
The IL-1 family member cytokine IL-36γ is recognised as key mediator in the immunopathology of psoriasis, hallmarks of which involve the activation of both resident and infiltrating inflammatory myeloid cells and aberrant angiogenesis. This research demonstrates a role for IL-36γ in both myeloid activation and angiogenesis. We show that IL-36γ induces the production of psoriasis-associated cytokines from macrophages (IL-23 and TNFα) and that this response is enhanced in macrophages from psoriasis patients...
2018: Frontiers in Immunology
Tuerhongjiang Tuxun, Shadike Apaer, Hai-Zhang Ma, Jin-Ming Zhao, Ren-Yong Lin, Tuerganaili Aji, Ying-Mei Shao, Hao Wen
Fluorodeoxyglucose (FDG) uptake by alveolar echinococcosis (AE) liver lesions is a signal of their metabolic activity and of disease progression. In order to find a surrogate marker for this status, we investigated whether parameters of the peripheral and/or periparasitic immune responses were associated with metabolic activity in a prospective case-control study of 30 AE patients and 22 healthy controls. Levels of 18 cytokines and chemokines, representative of innate and adaptive immune responses, were assessed in plasma and peripheral cells of two groups of patients with (MAAE) and without (MIAE) metabolically active lesions, and in the liver of MAAE patients...
March 13, 2018: Scientific Reports
Tingting Zheng, Weiheng Zhao, Hongjin Li, Shuxiu Xiao, Ran Hu, Miaomiao Han, Heng Liu, Yeqiang Liu, Kinya Otsu, Xinguang Liu, Gonghua Huang
Dendritic cells (DCs) contribute to psoriasis pathogenesis. In a mouse model of imiquimod-induced psoriasiform skin inflammation, we found that p38α activity in Langerhans cells (LCs), a skin-resident subset of DCs, promoted the generation of T cells that produce IL-17, a proinflammatory cytokine that is implicated in autoimmune disease. Deletion of p38α in LCs, but not in other skin or circulating DC subsets or T cells, decreased T cell-mediated psoriasiform skin inflammation in mice. The activity of p38α in LCs specifically promoted IL-17 production from γδ and CD4+ T cells by increasing the abundance of IL-23 and IL-6, two cytokines that stimulate IL-17 secretion...
March 13, 2018: Science Signaling
Jawad Bilal, Adam Berlinberg, Sandipan Bhattacharjee, Jaren Trost, Irbaz Bin Riaz, Drew J B Kurtzman
OBJECTIVE: To systematically analyze the efficacy and safety of interleukin (IL)-12/23, IL-17, and selective IL-23 inhibitors in moderate to severe plaque psoriasis. METHODS AND RESULTS: 24 randomized placebo-controlled trials were included. Compared to placebo, risk ratios (RR) of achieving PASI-75 and PGA/IGA 0/1 respectively were 20.20 (95% CI 13.82-29.54, p < 0.00001) and 14.55 (10.42-20.31, p < 0.00001) for ustekinumab 90mg, 13.75 (8.49-22.28, p < 0...
March 13, 2018: Journal of Dermatological Treatment
Yohei Mikami, Gianluca Scarno, Beatrice Zitti, Han-Yu Shih, Yuka Kanno, Angela Santoni, John J O'Shea, Giuseppe Sciumè
Innate lymphoid cells (ILCs) producing IL-22 and/or IL-17, designated as ILC3, comprise a heterogeneous subset of cells involved in regulation of gut barrier homeostasis and inflammation. Exogenous environmental cues in conjunction with regulated expression of endogenous factors are key determinants of plasticity of ILC3 towards the type 1 fate. Herein, by using mouse models and transcriptomic approaches, we defined at the molecular level, initial events driving ILC3 expressing natural cytotoxicity receptors (NCR+ ILC3) to acquire type 1 features...
March 9, 2018: European Journal of Immunology
Jessica E Weinstein, Kathryn L Pepple
PURPOSE OF REVIEW: Increasing evidence supports Th17 cells as key mediators of ocular inflammatory disease. Cytokines that are important for the development and pathologic function of these cells are potential therapeutic targets in patients with immune mediated uveitis. This review provides an overview of these cytokines including recent insights about their roles in ocular inflammation from laboratory and clinical studies. RECENT FINDINGS: Interleukin (IL)-6, IL-10, IL-17, IL-22, IL-23 and tumour necrosis factor-alpha (TNFα) are cytokines that have been examined for their functional role in uveitis and their relationship to pathologic Th17 cells...
March 6, 2018: Current Opinion in Ophthalmology
A T Hastie, C Steele, C W Dunaway, W C Moore, B M Rector, E Ampleford, H Li, L C Denlinger, N Jarjour, D A Meyers, E R Bleecker
BACKGROUND: The release of various inflammatory mediators into the bronchial lumen is thought to reflect both the type and degree of airway inflammation, eosinophilic Th2, and Th9, or neutrophilic Th1, and Th17, in patients with asthma. AIMS: We investigated whether cytokines and chemokines differed in sputum from subjects with more severe compared with milder asthma, and if unbiased factor analysis of cytokine and chemokine groupings indicates specific inflammatory pathways...
March 9, 2018: Clinical and Experimental Allergy: Journal of the British Society for Allergy and Clinical Immunology
Brinda Bhatt, Peng Zeng, Huabin Zhu, Sathish Sivaprakasam, Siyi Li, Haiyan Xiao, Lixin Dong, Pamela Shiao, Ravindra Kolhe, Nikhil Patel, Honglin Li, Daniel Levy-Bercowski, Vadivel Ganapathy, Nagendra Singh
A set of coordinated interactions between gut microbiota and the immune cells surveilling the intestine play a key role in shaping local immune responses and intestinal health. Gpr109a is a G protein-coupled receptor expressed at a very high level on innate immune cells and previously shown to play a key role in the induction of colonic regulatory T cells. In this study, we show that Gpr109a-/- Rag1-/- mice exhibit spontaneous rectal prolapse and colonic inflammation, characterized by the presence of an elevated number of IL-17-producing Rorγt+ innate lymphoid cells (ILCs; ILC3)...
March 7, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
Shankar Revu, Jing Wu, Matthew Henkel, Natalie Rittenhouse, Ashley Menk, Greg M Delgoffe, Amanda C Poholek, Mandy J McGeachy
Th17 cells drive autoimmune disease but also control commensal microbes. A common link among antigens from self-proteins or commensal microbiota is relatively low activation of T cell receptor (TCR) and costimulation signaling. Indeed, strong TCR/CD28 stimulation suppressed Th17 cell differentiation from human naive T cells, but not effector/memory cells. CD28 suppressed the classical Th17 transcriptional program, while inducing known Th17 regulators, and acted through an Akt-dependent mechanism. Th17 cells differentiated without CD28 were not anergic: they showed robust proliferation and maintained Th17 cytokine production following restimulation...
March 6, 2018: Cell Reports
Abbas Ahmadi-Vasmehjani, Rasoul Baharlou, Mohammad Reza Atashzar, Rahim Raofi, Mohammad Jafari, Faezeh-Sadat Razavi
Asthma prevalence and severity are greater in women than in men, and mounting evidence suggests this is in part related to female steroid sex hormones. Conflicting data are reported regarding pro- and anti-inflammatory properties of estradiol. This study was designed to clarify whether estradiol may contribute to enhanced T helper (Th) 17-associated cytokines production by peripheral blood mononuclear cells (PBMC) in asthmatic patients and healthy individuals. PBMCs from patients with asthma and healthy donors were cultured with 17-β estradiol (E2) and phytohemagglutinin (PHA)...
February 2018: Iranian Journal of Allergy, Asthma, and Immunology
Qin Zhu, Peifen Zheng, Xinyu Chen, Feng Zhou, Qiaona He, Yuefeng Yang
Ulcerative colitis (UC) is a chronic and nonspecific intestinal inflammatory disease, which may increase the risk of colon cancer. Andrographolide is a main active component of Andrographis paniculata . The anti-inflammatory ability of andrographolide suggested its potential therapeutic effect against UC. In the present study, elevated serum concentrations of proinflammatory factors, including (TNF)-α, interleukin (IL)-1β, IL-6 and IL-23, as well as increased percentages of Th17 cells (IL-17+CD4+ cells) in CD4+ cells were detected in UC patients compared to that in healthy donors...
2018: American Journal of Translational Research
Sauzanne Khalilieh, Peter Hodsman, Christine Xu, Anjela Tzontcheva, Shirley Glasgow, Diana Montgomery
Tildrakizumab, a high-affinity humanized IgG1k antibody that selectively binds interleukin (IL)-23 p19 subunit of cytokine IL-23 and neutralizes its function, is under investigation for treatment of moderate-to-severe chronic plaque psoriasis. The objective of this analysis was to assess the pharmacokinetics (PK), bioavailability and safety/tolerability of single ascending doses of tildrakizumab following intravenous (IV) and subcutaneous (SC) dosing in healthy subjects. P05661 was a phase 1, single dose, randomized, placebo-controlled study of tildrakizumab IV doses of 0...
March 6, 2018: Basic & Clinical Pharmacology & Toxicology
Yuzhu Hou, Linnan Zhu, Hongling Tian, Hai-Xi Sun, Ruoyu Wang, Lianfeng Zhang, Yong Zhao
Macrophages acquire distinct phenotypes during tissue stress and inflammatory responses. Macrophages are roughly categorized into two different subsets named inflammatory M1 and anti-inflammatory M2 macrophages. We herein identified a unique pathogenic macrophage subpopulation driven by IL-23 with a distinct gene expression profile including defined types of cytokines. The freshly isolated resting mouse peritoneal macrophages were stimulated with different cytokines in vitro, the expression of cytokines and chemokines were detected by microarray, real-time PCR, ELISA and multiple colors flow cytometry...
March 5, 2018: Protein & Cell
Dulshara Sachini Amarasekara, Hyeongseok Yun, Sumi Kim, Nari Lee, Hyunjong Kim, Jaerang Rho
Cytokines play a pivotal role in maintaining bone homeostasis. Osteoclasts (OCs), the sole bone resorbing cells, are regulated by numerous cytokines. Macrophage colony-stimulating factor and receptor activator of NF-κB ligand play a central role in OC differentiation, which is also termed osteoclastogenesis. Osteoclastogenic cytokines, including tumor necrosis factor-α, IL-1, IL-6, IL-7, IL-8, IL-11, IL-15, IL-17, IL-23, and IL-34, promote OC differentiation, whereas anti-osteoclastogenic cytokines, including interferon (IFN)-α, IFN-β, IFN-γ, IL-3, IL-4, IL-10, IL-12, IL-27, and IL-33, downregulate OC differentiation...
February 2018: Immune Network
Na Li, Wenwen Xu, Ying Yuan, Natarajan Ayithan, Yasutomo Imai, Xuesong Wu, Halli Miller, Michael Olson, Yunfeng Feng, Yina H Huang, Mary Jo Turk, Samuel T Hwang, Subramaniam Malarkannan, Li Wang
A correction has been published and is linked to the HTML and PDF versions of this paper. The error has not been fixed in the paper.
March 1, 2018: Scientific Reports
Lin-Li Chang, Wen-Hung Hsu, Mou-Chieh Kao, Chih-Chung Chou, Chung-Cheng Lin, Chung-Jung Liu, Bi-Chuang Weng, Fu-Chen Kuo, Chao-Hung Kuo, Ming-Hong Lin, Chun-Jen Wang, Chun-Hung Lin, Deng-Chyang Wu, Shau-Ku Huang
Tissue stroma is known to be important in regulating Hp-mediated inflammation, but its interaction with Hp and dendritic cells (DCs) remains to be determined. To this end, the potential crosstalk between H. pylori (Hp) infected gastric stromal cells (Hp-GSCs) and DCs was investigated. Primary GSCs from cancerous and adjacent normal tissues were generated from gastric cancer patients, and monocyte-derived DCs were obtained from healthy individuals. Levels of cytokines and prostaglandin E2 (PGE2 ) were measured by ELISA, and C-type lectin expression in GSCs was assessed by flow cytometry and immunohistochemistry...
February 28, 2018: Scientific Reports
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