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Enzhuo Yang, Rui Yang, Ming Guo, Dan Huang, Wandang Wang, Zhuoran Zhang, Crystal Chen, Feifei Wang, Wenzhe Ho, Ling Shen, Heping Xiao, Zheng W Chen, Hongbo Shen
Tuberculosis (TB) has become the most deadly infectious diseases due to epidemics of HIV/AIDS and multidrug-resistant/extensively drug-resistant TB (MDR-/XDR-TB). Although person-to-person transmission contributes to MDR-TB, it remains unknown whether infection with MDR strains resembles infection with drug-sensitive (DS) TB strains, manipulating limited or broad immune responses. To address these questions, macaques were infected with MDR strain V791 and a drug-sensitive Erdman strain of TB. MDR bacilli burdens in the airway were significantly higher than those of the Erdman control after pulmonary exposure...
December 12, 2018: Emerging Microbes & Infections
Helen He, Emma Guttman-Yassky
Atopic dermatitis (AD) is one of the most common inflammatory skin diseases. AD is driven by barrier dysfunction and abnormal immune activation of T helper (Th) 2, Th22, and varying degrees of Th1 and Th17 among various subtypes. The Janus kinase (JAK)-signal transducer and activator of transcription (STAT) and spleen tyrosine kinase (SYK) pathways are involved in signaling of several AD-related cytokines, such as IFN-γ, IL-4, IL-13, IL-31, IL-33, IL-23, IL-22, and IL-17, mediating downstream inflammation and barrier alterations...
December 7, 2018: American Journal of Clinical Dermatology
Eric Simpson, Shinichi Imafuku, Yves Poulin, Benjamin Ungar, Lisa Zhou, Kunal Malik, Huei-Chi Wen, Hui Xu, Yeriel D Estrada, Xiangyu Peng, Mindy Chen, Nilam Shah, Mayte Suarez-Farinas, Ana B Pavel, Kristine Nograles, Emma Guttman-Yassky
BACKGROUND: and Purpose: A phase 2, double-blind, placebo-controlled trial evaluated apremilast efficacy, safety, and pharmacodynamics in adults with moderate to severe atopic dermatitis (AD). STUDY DESIGN: and Methods: Patients were randomized to placebo, apremilast 30 mg BID (APR30), or apremilast 40 mg BID (APR40) for 12 weeks. During Weeks 12-24, all patients received APR30 or APR40. A biopsy substudy evaluated AD-related biomarkers. RESULTS: Among 185 randomized intent-to-treat patients at Week 12, a dose-response relationship was observed; APR40 (n=63), but not APR30 (n=58), led to statistically significant improvements (vs...
December 5, 2018: Journal of Investigative Dermatology
Feng-Xia Zhan, Juan Li, Min Fang, Juan Ding, Qian Wang
BACKGROUND The disequilibrium of T helper (Th) cells play an important role in the occurrence and development of immune thrombocytopenic purpura (ITP). Th22 cells, as a newly discovered subset of T lymphocytes, plays an important role in autoimmune disorders and inflammatory diseases. MATERIAL AND METHODS This study explored the role of different lymphocyte subsets in chronic ITP. To explore the value of Th22 cells in the diagnosis of ITP, the numbers of Th1, Th17, and Th22 cells were detected by a 4-color flow cytometric in 32 chronic ITP patients and 30 healthy controls...
December 4, 2018: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
Yoshito Yamada, Karina Brüstle, Wolfgang Jungraithmayr
BACKGROUND: Human lung transplantation has evolved to an established treatment for pulmonary diseases in their end stages; however, the long-term outcome is worse when compared to all other solid transplantable organs. The major reason for this unfavorable outcome is rejection, either in its acute or chronic form, the latter termed as chronic lung allograft dysfunction. METHODS: A systematic review search was performed. RESULTS: One of the most important immune cells responsible for rejection are T cells...
January 2019: Journal of Surgical Research
Jakub Ruszkowski, Katarzyna A Lisowska, Małgorzata Pindel, Zbigniew Heleniak, Alicja Dębska-Ślizień, Jacek M Witkowski
BACKGROUND: Immunoglobulin A nephropathy (IgAN), the most frequent cause of primary glomerulonephritis worldwide, is an autoimmune disease with complex pathogenesis. In this review, we focus on T cells and summarize knowledge about their involvement in pathophysiology and treatment of IgAN METHODS: We reviewed the literature for (1) alterations of T cell subpopulations in IgAN, (2) experimental and clinical proofs for T cells' participation in IgAN pathogenesis, (3) clinical correlations with T cell-associated alterations, and (4) influence of drugs used in IgAN therapy on T cell subpopulations...
November 7, 2018: Clinical and Experimental Nephrology
Yue Zheng, Tong Li
Interleukin -22 (IL-22) is a member of interleukin-10 (IL-10) family cytokines that is produced by different types of lymphocytes included in both innate and adaptive immune systems. These lymphocytes include activated T cells, most notably Th17 and Th22 cells, as well as NK cells, γδ T cells, etc. IL-22 mediate its effects via the IL-22-IL-22R complex and subsequent Janus Kinase-signal transduces and activators transcription (JAK-STAT) signaling pathway. According to recent evidence, IL-22 played a critical role in the pathogenesis of many non-autoimmune diseases...
October 18, 2018: Human Vaccines & Immunotherapeutics
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 the skin of AA patients as compared with that of EA AD and healthy controls...
September 14, 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-4 receptor α mAb inhibiting signaling of IL-4 and IL-13, key drivers of type 2-driven inflammation, as demonstrated by its efficacy in patients with atopic/allergic diseases. OBJECTIVE: This placebo-controlled, double-blind trial (NCT01979016) evaluated the efficacy, safety, and effects of dupilumab on molecular/cellular lesional and nonlesional skin phenotypes and systemic type 2 biomarkers of patients with moderate-to-severe atopic dermatitis (AD)...
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 an aberrance of CD4+ helper and regulatory T cells and comprises histopathologically chronic active enterocolitis with features reflecting both activity and chronicity of mucosal inflammation. The exact immunological-histological correlation in IBD is not understood. Methods: We studied the correlation between colonic mucosal CD4+ T cell subsets [Th1, Th2, Th17, Th22 and Treg] and mucosal histological changes in ulcerative colitis [UC] and Crohn's disease [CD]...
November 28, 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
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