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Emma Guttman-Yassky, Jon M Hanifin, Mark Boguniewicz, Andreas Wollenberg, Robert Bissonnette, Vivek Purohit, Iain Kilty, Anna M Tallman, Michael A Zielinski
Atopic dermatitis (AD) is a highly prevalent, chronic inflammatory skin disease that affects children and adults. The pathophysiology of AD is complex and involves skin barrier and immune dysfunction. Many immune cytokine pathways are amplified in AD, including T helper (Th) 2, Th22, Th17 and Th1. Current treatment guidelines recommend topical medications as initial therapy; however, until recently, only two drug classes were available: topical corticosteroids (TCSs) and topical calcineurin inhibitors (TCIs)...
October 17, 2018: Experimental Dermatology
Katharina Ronacher, Roma Sinha, Michelle Cestari
Approximately 10% of individuals latently infected with Mycobacterium tuberculosis (Mtb) develop active tuberculosis (TB) during their lifetime. Although it is well recognized that T-helper 1 immune responses are crucial for containing latent TB infection, the full array of host factors conferring protective immunity from TB progression are not completely understood. IL-22 is produced by cells of the innate and adaptive immune system including innate lymphoid cells, and natural killer cells as well as T lymphocytes (Th1, Th17, and Th22) and binds to its cognate receptor, the IL-22R1, which is expressed on non-hematopoietic cells such as lung epithelial cells...
2018: Frontiers in Immunology
Jing Ye, Yuan Wang, Zhen Wang, Qingwei Ji, Ying Huang, Tao Zeng, Haiying Hu, Di Ye, Jun Wan, Yingzhong Lin
Background: Previous studies demonstrated that the subsets of CD4+ T helper (Th) cells are closely related to vascular diseases, including atherosclerosis and hypertension. This study is aimed at investigating the circulating Th1, Th2, Th9, Th17, Th22, and Treg levels in aortic dissection (AD) patients. Methods: Blood samples from AD ( n = 56) and non-AD (NAD, n = 24) patients were collected, and the circulating levels of Th1, Th2, Th9, Th17, Th22, and Treg cells and their transcription factors and functional cytokines were measured by flow cytometric analysis, quantitative polymerase chain reaction, and enzyme-linked immunosorbent assays, respectively...
2018: Mediators of Inflammation
Xian-Wen Yang, Hai-Xing Jiang, Ronge Lei, Wei-Shun Lu, Shi-Hui Tan, Shan-Yu Qin
T helper (Th)22 and Th17 cells are implicated in the pathogenesis of a number of types of cancer. However, the function of Th22 and Th17 cells in malignant ascites (MA) remains unknown. The present study aimed at examining the distribution, phenotypes, recruitment, and prognostic value of Th22 and Th17 cells in MA from patients with hepatocellular carcinoma (HCC). A total of 26 patients with HCC with MA and 15 healthy controls were included in the present study. The proportion of Th22 cells, Th17 cells, C-C motif chemokine receptor (CCR)4, CCR6 and CCR10 were examined using flow cytometry...
October 2018: Oncology Letters
Abdollah Jafarzadeh, Maryam Nemati
Multiple sclerosis (MS) is characterized by chronic inflammatory response-induced demyelination of the neurons and degeneration of the axons within the central nervous system (CNS). A complex network of immunopathological-, inflammatory- and oxidative parameters involve in the development and advancement of MS. The anti-inflammatory, immunomodulatory and anti-oxidative characteristics of the ginger and several of its components have been indicated in some of experimental and clinical investigations. The possible therapeutic potentials of ginger and its ingredients in the treatment of MS may exert mainly through the regulation of the Th1-, Th2-, Th9-, Th17-, Th22- and Treg cell-related immune responses, down-regulation of the B cell-related immune responses, modulation of the macrophages-related responses, modulation of the production of pro- and anti-inflammatory cytokines, down-regulation of the arachidonic acid-derived mediators, interfering with the toll like receptor-related signaling pathways, suppression of the inflammasomes, down-regulation of the oxidative stress, reduction of the adhesion molecules expression, and down-regulation of the expression of the chemokines and chemokine receptors...
November 15, 2018: Journal of Neuroimmunology
Riana D Sanyal, Ana B Pavel, Jacob Glickman, Tom C Chan, Xiuzhong Zheng, Ning Zhang, Inna Cueto, Xiangyu Peng, Yeriel Estrada, Judilyn Fuentes-Duculan, Andrew F Alexis, James G Krueger, Emma Guttman-Yassky
BACKGROUND: African Americans/(AA) are disproportionately impacted by atopic dermatitis/(AD) with increased prevalence and therapeutic challenges unique to this population. Molecular profiling data informing development of targeted therapeutics for AD are derived primarily from European American/(EA) patients. These studies are absent in AA, hindering development of effective treatments for this population. OBJECTIVE: We sought to characterize the global molecular profile of AD in skin of AA patients as compared with that of EA AD and healthy controls...
September 6, 2018: Annals of Allergy, Asthma & Immunology
Stephanie M Rangel, Amy S Paller
Staphylococcus aureus infection is a major burden for individuals with moderate-to-severe atopic dermatitis and a known inducer of disease exacerbation. This increased susceptibility to staphylococcal infections has been attributed to abnormalities in the innate immune system of atopic dermatitis (AD) skin, including deficits in barrier proteins and lipids, and a muted response in generating antimicrobial peptides, all of which is further impaired by the activation of Th2 and Th22 immune pathways, which characterizes AD...
September 2018: Clinics in Dermatology
Emma Guttman-Yassky, Robert Bissonnette, Benjamin Ungar, Mayte Suárez-Fariñas, Marius Ardeleanu, Hitokazu Esaki, Maria Suprun, Yeriel Estrada, Hui Xu, Xiangyu Peng, Jonathan I Silverberg, Alan Menter, James G Krueger, Rick Zhang, Usman Chaudhry, Brian Swanson, Neil M H Graham, Gianluca Pirozzi, George D Yancopoulos, Jennifer D D Hamilton
BACKGROUND: Dupilumab is an IL-4Rα monoclonal antibody inhibiting signaling of IL-4/IL-13, key drivers of Type 2-driven inflammation, as demonstrated by its efficacy in atopic/allergic diseases. OBJECTIVE: This placebo-controlled, double-blind trial (NCT01979016) evaluated efficacy, safety, and effects of dupilumab on molecular/cellular lesional and nonlesional skin phenotypes and systemic Type 2 biomarkers of moderate-to-severe atopic dermatitis (AD) patients...
September 5, 2018: Journal of Allergy and Clinical Immunology
D-P Chen, S-H Hou, Y-G Chen, M-S Chen, Z-Z Hu, Z-J Zhang
OBJECTIVE: L-3-n-butylphthalide (L-NBP) is a type of anti-ischemic cranial nerve protective drug that may act on vascular dementia (VD). Phosphatidylinositol-3 kinase (PI3K)/protein kinase B (AKT/PKB) signaling pathway can up-regulate B-cell lymphoma 2 (Bcl-2) expression, reduce reactive oxygen species (ROS) production, and alleviate cell apoptosis. This study aimed at investigating the role of L-NBP on neurological function and cell apoptosis in VD mouse through regulating PI3K/AKT signaling pathway...
August 2018: European Review for Medical and Pharmacological Sciences
Xianyong Gui, Ji Li, Aito Ueno, Marietta Iacucci, Jiaming Qian, Subrata Ghosh
Background: Inflammatory bowel disease (IBD) results particularly from aberrance of CD4+ helper and regulatory T cells and is histopathologically chronic active enterocolitis with features reflecting both activity and chronicity of mucosal inflammation. The exact immunologic-histologic correlation is not understood. Methods: We studied the correlation between colonic mucosal CD4+ T cell subsets (Th1, Th2, Th17, Th22, and Treg) and mucosal histologic changes in ulcerative colitis (UC) and Crohn's disease (CD)...
August 20, 2018: Journal of Crohn's & Colitis
Patrick M Brunner, Ana B Pavel, Saakshi Khattri, Alexandra Leonard, Kunal Malik, Sharon Rose, Shelbi Jim On, Anjali S Vekaria, Claudia Traidl-Hoffmann, Giselle K Singer, Danielle Baum, Patricia Gilleaudeau, Mary Sullivan-Whalen, Judilyn Fuentes-Duculan, Xuan Li, Xiuzhong Zheng, Yeriel Estrada, Sandra Garcet, Huei-Chi Wen, Juana Gonzalez, Israel Coats, Inna Cueto, Avidan U Neumann, Mark G Lebwohl, James G Krueger, Emma Guttman-Yassky
BACKGROUND: IL-22 is potentially a pathogenic cytokine in patients with atopic dermatitis (AD), but the molecular effects of IL-22 antagonism have not been defined in human subjects. OBJECTIVE: We sought to evaluate the cellular and molecular effects of IL-22 blockade in tissues from patients with moderate-to-severe AD. METHODS: We assessed lesional and nonlesional skin from 59 patients with moderate-to-severe AD treated with anti-IL-22 (fezakinumab) versus placebo (2:1) using transcriptomic and immunohistochemistry analyses...
August 17, 2018: Journal of Allergy and Clinical Immunology
A Claßen, T Buhl, S Schubert, M Worm, A Bauer, J Geier, S Molin
BACKGROUND: Earlier studies suggested an inverse association between contact allergy and psoriasis, although the results of clinical studies have been inconsistent. Gene expression studies in human contact allergy focusing on immune responses revealed nickel being an inducer of T helper (Th)1/Th17 and some Th22 immune polarization, whereas fragrances were found to promote a Th2-dominated immune activation. OBJECTIVES: To investigate the epidemiological association between contact allergy and psoriasis in a large multicentre cohort and to analyse the sensitization profile to specific allergens in these patients...
August 12, 2018: British Journal of Dermatology
Shuqian Wang, Yinan Yao, Minya Yao, Peifen Fu, Weilin Wang
PURPOSE: Owing to the absence of any targeted therapies, triple negative breast cancer (TNBC), which accounts for approximately 15% of all breast cancers, typically have a poorer outcome. In an attempt to find out the TNBCs' microenvironment, we ran into the endogenous expression of a newly discovered cytokine known as Interleukin (IL)-22. METHODS: Thirty TNBC patients were recruited and the levels of IL-22 producing (Th22) cells in tumor, paratumor and normal breast tissues were measured...
September 10, 2018: Biochemical and Biophysical Research Communications
Éric Toussirot, Caroline Laheurte, Béatrice Gaugler, Damien Gabriel, Philippe Saas
The IL-23/T helper 17 (Th17) axis plays an important role in joint inflammation in ankylosing spondylitis (AS). Conventional CD4+ Th17 cells are a major source of IL-17A. IL-22 is another cytokine implicated in AS pathophysiology and is produced by Th17 and Th22 cells. In this study, we aimed to analyze conventional and non-conventional T cell subsets producing IL-17A and IL-22 in patients with AS. We thus evaluated the intracellular staining for IL-17A, IL-22, and IFN-γ in peripheral blood mononuclear cells of 36 patients with AS and 55 age- and sex-matched healthy controls (HC)...
2018: Frontiers in Immunology
Ma Liang, Zhang Liwen, Zhuang Yun, Ding Yanbo, Chen Jianping
This study is aimed at examining the potential role of regulatory T- (Treg-) Th1-Th17-Th22 cells in the pathogenic process of autoimmune hepatitis (AIH). The numbers of Foxp3+ Tregs and Th1, Th17, and Th22 cells were measured in 32 AIH patients using flow cytometry. Moreover, a murine model of experimental autoimmune hepatitis (EAH) was also established and used to investigate the function of Treg-Th1-Th17-Th22 cells in disease progression. AIH patients undergoing an active state had significantly decreased numbers of CD3+ CD4+ CD25+ Foxp3+ Tregs and increased numbers of CD3+ CD4+ CD25- Foxp3+ T, CD3+ CD4+ IFN- γ + Th1, CD3+ CD4+ IL-17+ Th17, and CD3+ CD4+ IL-2+ Th22 cells as well as higher levels of Th1/Th17/Th22-type cytokines compared to AIH patients in remission and HC...
2018: Journal of Immunology Research
Cristina Albanesi, Stefania Madonna, Paolo Gisondi, Giampiero Girolomoni
Psoriasis is a chronic inflammatory skin disease resulting from genetic, epigenetic, environmental, and lifestyle factors. To date, several immunopathogenic mechanisms of psoriasis have been elucidated, and, in the current model, the cross talk between autoreactive T cells and resident keratinocytes generates inflammatory and immune circuits responsible for the initiation, progression, and persistence of the disease. Several autoantigens derived from keratinocytes (i.e., LL37 cathelecidin/nucleic acid complexes, newly generated lipid antigens) have been identified, which may trigger initial activation of T cells, particularly IL-17-producing T cells, T helper (Th)1 and Th22 cells...
2018: Frontiers in Immunology
Farinaz Behfarjam, Zohreh Jadali
BACKGROUND Previous studies have indicated an elevated level of serum Interleukin (IL)-22 in patients with autoimmune hepatitis (AIH). However, there are no experimental data on the master transcription factor (aryl hydrocarbon receptor) that plays an important role in the development of T helper type 22 (Th22) cells as major producers of IL-22. The aim of the present study was to examine the expression of aryl hydrocarbon receptor in patients with AIH and in normal controls. METHODS Levels of mRNA transcripts were measured in the peripheral blood mononuclear cells of 18 patients with AIH and compared with 18 normal controls by a quantitative real-time polymerase chain reaction...
April 2018: Middle East Journal of Digestive Diseases
Lies Hulshof, Saskia A Overbeek, Anne L Wyllie, Mei Ling J N Chu, Debby Bogaert, Wilco de Jager, Leon M J Knippels, Elisabeth A M Sanders, Wim M C van Aalderen, Johan Garssen, Belinda Van't Land, Aline B Sprikkelman
Background: Atopic dermatitis (AD) is the most common chronic inflammatory skin disease in infancy with a complex pathology. In adults, the clinical severity of AD has been associated with increases in T helper cell type (Th) 2, Th22, and Th17 serum markers, including high levels of CC chemokine ligand (CCL) 17 and CCL22 chemokines. Objective: To explore the possible association between serum chemokine levels and AD severity in infants with moderate-to-severe AD and elevated immunoglobulin E (IgE)...
2018: Frontiers in Immunology
Xuehua Chen, Yanfu Wang, Jiali Wang, Jinhui Wen, Xuzhao Jia, Xiaojun Wang, Hua Zhang
Chronic inflammation and immunosuppression lead to aging and tumorigenesis. T-helper 22 (Th22) cells, interleukin 22 (IL-22) and myeloid-derived suppressor cells (MDSCs) serve an important role in inflammatory-immune diseases and cancer. However, the status of Th22 cells, IL-22 and MDSCs in aging and elderly gastric cancer progression is unknown. In the present study, 39 elderly patients with gastric cancer (EGC), 32 elderly healthy controls (HE) and 31 young healthy controls (HY) were enrolled, and the peripheral Th22, Th17 and Th1 cells, and MDSCs, were examined using flow cytometry...
July 2018: Oncology Letters
Juan Manuel Leyva-Castillo, Juhan Yoon, Raif S Geha
BACKGROUND: Serum IL-22 levels are increased in patients with atopic dermatitis, which commonly precedes asthma in the atopic march. Epicutaneous sensitization in mice results in TH 2-dominated skin inflammation that mimics atopic dermatitis and sensitizes the airways for antigen challenge-induced allergic inflammation characterized by the presence of both eosinophils and neutrophils. Epicutaneous sensitization results in increased serum levels of IL-22. OBJECTIVE: We sought to determine the role of IL-22 in antigen-driven airway allergic inflammation after inhalation challenge in epicutaneously sensitized mice...
June 18, 2018: Journal of Allergy and Clinical Immunology
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