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Lisa Strohbuecker, Hans Koenen, Esther van Rijssen, Bram van Cranenbroek, Esther Fasse, Irma Joosten, Andreas Körber, Christoph Bergmann
Purpose: Psoriasis vulgaris (PV) is an autoimmune-related chronic inflammatory disease of the skin, with both vascular and metabolic effects. Aggravating factors have been identified that initiate and maintain inflammation, including expression of Th1-, Th17-, and Th22-cell derived cytokines. Recently, we showed that the evolutionarily ancient and highly conserved damage-associated molecular pattern molecule "high mobility group box 1 (HMGB1)" is significantly increased in the serum of PV patients with disease progression and is decreased under standard therapies...
2019: Psoriasis: Targets and Therapy
Choong-Gu Lee, Ho-Keun Kwon, Hyeji Kang, Young Kim, Jong Hee Nam, Young Ho Won, Sunhee Park, Taemook Kim, Keunsoo Kang, Dipayan Rudra, Chang-Duk Jun, Zee Yong Park, Sin-Hyeog Im
Atopic dermatitis (AD) is a complex inflammatory skin disease mediated by immune cells of both adaptive and innate types. Among them, CD4+ Th cells are one of major players of AD pathogenesis. Although the pathogenic role of Th2 cells has been well characterized, Th17/Th22 cells are also implicated in the pathogenesis of AD. However, the molecular mechanisms underlying pathogenic immune responses in AD remain unclear. We sought to investigate how the defect in the AD susceptibility gene, Ets1, is involved in AD pathogenesis in human and mice and its clinical relevance in disease severity by identifying Ets1 target genes and binding partners...
March 7, 2019: JCI Insight
Mikhaïl A Van Herck, Jonas Weyler, Wilhelmus J Kwanten, Eveline L Dirinck, Benedicte Y De Winter, Sven M Francque, Luisa Vonghia
Non-alcoholic fatty liver disease (NAFLD) constitutes a spectrum of disease states characterized by hepatic steatosis and is closely associated to obesity and the metabolic syndrome. In non-alcoholic steatohepatitis (NASH), additionally, inflammatory changes and hepatocellular damage are present, representing a more severe condition, for which the treatment is an unmet medical need. Pathophysiologically, the immune system is one of the main drivers of NAFLD progression and other obesity-related comorbidities, and both the innate and adaptive immune system are involved...
2019: Frontiers in Immunology
Stephen Lai, Carly E Starke, Jacob K Flynn, Carol L Vinton, Alexandra M Ortiz, Joseph C Mudd, Jason M Brenchley
Among the numerous immunological abnormalities observed in chronically HIV-infected individuals, perturbations in memory CD4 T cells are thought to specifically contribute to disease pathogenesis. Among these, functional imbalance in the frequencies of T-regulatory (Tregs) and Interleukin-17/22 (IL-17/IL-22) producing T-helper cells (Th17/Th22) from mucosal sites, and T-follicular helper cells (Tfh) in lymph nodes, are thought to facilitate specific aspects of disease pathogenesis. However, while preferential infection of Tfh cells is widely believed to create an important viral reservoir in an immunologically privileged site in vivo , whether immunological perturbations among memory CD4 T cell populations are attributable to their relative infectivity by the virus in vivo is unclear...
February 20, 2019: Journal of Virology
Shanyu Qin, Mei Chen, Xiaoyun Guo, Wei Luo, Jiaxu Wang, Haixing Jiang
BACKGROUND: Th22 cells are a recently identified CD4+ T helper subset and have been implicated in the pathogenesis of certain diseases in humans, but the role of Th22 cells in liver cirrhosis (LC) remains unclear. OBJECTIVES: The aim of the study was to investigate the expression and clinical significance of intrahepatic Th22 cells in LC tissues. MATERIAL AND METHODS: Samples of liver tissue of 20 LC patients and 12 normal controls (NC) were collected...
February 8, 2019: Advances in Clinical and Experimental Medicine: Official Organ Wroclaw Medical University
Emma Guttman-Yassky, Ana B Pavel, Lisa Zhou, Yeriel D Estrada, Ning Zhang, Hui Xu, Xiangyu Peng, Huei-Chi Wen, Panayiota Govas, Girish Gudi, C A Vinu, Hui Fang, Yacine Salhi, Jonathan Back, Venkateshwar Reddy, Robert Bissonnette, Catherine Maari, Fred Grossman, Gerhard Wolff
BACKGROUND: GBR 830 is a humanized, monoclonal antibody against OX40, a co-stimulatory receptor on activated T-cells. OX40 inhibition may have a therapeutic role in T-cell-mediated diseases, including atopic dermatitis (AD). OBJECTIVE: This exploratory phase 2a study investigated safety, efficacy, and tissue effects of GBR 830 in AD. METHODS: Moderate-to-severe AD subjects (affected body-surface area ≥10%, Eczema Area and Severity Index [EASI] ≥12, inadequate response to topical treatments) were randomized 3:1 to intravenous GBR 830 10 mg/kg or placebo on Day 1/baseline and Day 29...
February 6, 2019: Journal of Allergy and Clinical Immunology
Charlotte M Mousset, Willemijn Hobo, Rob Woestenenk, Frank Preijers, Harry Dolstra, Anniek B van der Waart
The T cell compartment can form a powerful defense against extrinsic (e.g., pathogens) and intrinsic danger (e.g., malignant cells). At the same time, specific subsets of T cells control this process to keep the immune system in check and prevent autoimmunity. A wide variety in T cell functionalities exists, which is dependent on the differentiation and maturation state of the T cells. In this review, we report an overview for the identification of CD4+ T-αβ cells (T-helper (Th)1, Th2, Th9, Th17, Th22, and CD4+ regulatory T cells), CD8+ T-αβ cells (cytotoxic T lymphocyte (Tc)1, Tc2, Tc9, Tc17, and CD8+ regulatory T cells), and their additional effector memory status (naïve, stem cell memory, central memory, effector memory, and effector) using flow cytometry...
February 4, 2019: Cytometry. Part A: the Journal of the International Society for Analytical Cytology
Justyna Luty, Katarzyna Ruckemann-Dziurdzińska, Jacek M Witkowski, Ewa Bryl
Autoimmune thyroid disease (ATD) is a chronic autoimmune thyroiditis with a complex pathogenesis including environmental factors, genetic background and immune system actions. Despite the large-scale research and discovery of new subpopulations of lymphocytes, cytokines, chemokines and their functions in the human body, the ethiology of ATD in many aspects remains a mystery. This article tries to summarize mostly the immunological aspects of this disease, including the roles of different cells types (dendritic cells, B cells, CD4+ and CD8+ T cells, NK cells and regulatory T cells) and of different cytokines (secreted by Th1/Th2/Th17/Th22 lymphocyte subpopulations and other, including the IL-23 and CXCL10)...
January 31, 2019: Cytokine
Maria Alexandra Rodrigues, Tiago Torres
INTRODUCTION: Atopic dermatitis (AD) is the most common chronic inflammatory skin disease. Lesional skin of AD contains elevated levels of Th2, Th17, Th22 and Th1-citokines. With a growing movement towards use of targeted therapies, parallel to psoriasis, JAK inhibitors are an important focus of therapeutic research for AD. METHODS: We review current evidence on the efficacy and safety of oral and topical JAK inhibitors for the treatment of AD. RESULTS: Several JAK inhibitors are in phase II and III clinical trials as oral therapies for moderate-to-severe AD or as topical treatments for mild-to-moderate AD...
January 31, 2019: Journal of Dermatological Treatment
Randall Li, Suhail Hadi, Emma Guttman-Yassky
Atopic dermatitis (AD) is the most common inflammatory skin disease, yet until recently there were no safe systemic therapies approved for the long-term management of AD in adult patients. A deeper understanding of disease pathogenesis and identification of molecular and cellular changes has resulted in a rapidly evolving pipeline of therapeutics that holds promise for safer long-term control. Areas Covered: In this review, we highlight the growing arsenal of biologic and small molecule antagonists that target pathways implicated in AD pathogenesis...
January 23, 2019: Expert Opinion on Biological Therapy
Stefania Croci, Martina Bonacini, Francesco Muratore, Andrea Caruso, Antonio Fontana, Luigi Boiardi, Alessandra Soriano, Alberto Cavazza, Luca Cimino, Lucia Belloni, Ori Perry, Mati Fridkin, Maria Parmeggiani, Miri Blank, Yehuda Shoenfeld, Carlo Salvarani
Tuftsin-PhosphorylCholine (TPC) is a novel bi-specific molecule which links tuftsin and phosphorylcholine. TPC has shown immunomodulatory activities in experimental mouse models of autoimmune diseases. We studied herein the effects of TPC ex vivo on both peripheral blood mononuclear cells (PBMCs) and temporal artery biopsies (TABs) obtained from patients with giant cell arteritis (GCA) and age-matched disease controls. GCA is an immune-mediated disease affecting large vessels. Levels of 18 cytokines in supernatants, PBMC viability, T helper (Th) cell differentiation of PBMCs and gene expression in TABs were analyzed...
January 9, 2019: Journal of Autoimmunity
Mirim Jin, Juhan Yoon
Atopic dermatitis (AD) is the most common pruritic inflammatory skin disease characterized by thickening of epidermis and dermis as well as by the infiltration of multiple pathogenic polarized T lymphocytes, including Th2, Th17, and Th22 cells. Significant progress has been made to develop targeted therapeutics for treating AD, e.g., Food and Drug Administration-approved dupilumab, an antibody for dual targeting of IL-4 and IL-13 signaling pathways. Additionally, a growing body of published evidence and a promising result from the early stage of the clinical trial with ILV-094, an anti-IL-22 antibody, strongly support the notion that IL-22 is a potential therapeutic target for treating AD...
December 2018: Immune Network
Tali Czarnowicki, Helen He, Alexandra Leonard, Hyun Je Kim, Naoya Kameyama, Ana B Pavel, Randall Li, Yeriel Estrada, Huei-Chi Wen, Grace W Kimmel, Hee J Kim, Margot Chima, Mark Lebwohl, James G Krueger, Emma Guttman-Yassky
BACKGROUND: Peripheral blood skin-homing/cutaneous lymphocyte antigen (CLA)+ T cells emerge as biomarkers of cutaneous immune activation in patients with inflammatory skin diseases (atopic dermatitis [AD] and alopecia areata [AA]). However, blood phenotyping across these subsets is not yet available in patients with vitiligo. OBJECTIVE: We sought to measure cytokine production by circulating skin-homing (CLA+ ) versus systemic (CLA- ) "polar" CD4+ /CD8+ ratio and activated T-cell subsets in patients with vitiligo compared with patients with AA, AD, or psoriasis and control subjects...
December 18, 2018: Journal of Allergy and Clinical Immunology
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
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