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Th2- type allergic diseases

Matthew C Altman, Elizabeth Whalen, Alkis Togias, George T O'Connor, Leonard B Bacharier, Gordon R Bloomberg, Meyer Kattan, Robert A Wood, Scott Presnell, Petra LeBeau, Katy Jaffee, Cynthia M Visness, William W Busse, James E Gern
BACKGROUND: Childhood asthma in inner city populations is a major public health burden and understanding early life immune mechanisms that promote asthma onset is key to disease prevention. Children who develop asthma demonstrate a high prevalence of aeroallergen sensitization and T helper 2 (Th2)-type inflammation, however the early life immune events that lead to Th2 skewing and disease development are unknown. OBJECTIVE: We sought to use RNA sequencing of peripheral blood mononuclear cells (PBMCs) collected at age 2 to determine networks of immune responses that occur in children who develop allergy and asthma...
March 5, 2018: Journal of Allergy and Clinical Immunology
Raffaela Zaffini, Giovanni Gotte, Marta Menegazzi
Asthma is a chronic lung disease affecting people of all ages worldwide, and it frequently begins in childhood. Because of its chronic nature, it is characterized by pathological manifestations, including airway inflammation, remodeling, and goblet cell hyperplasia. Current therapies for asthma, including corticosteroids and beta-2 adrenergic agonists, are directed toward relieving the symptoms of the asthmatic response, with poor effectiveness against the underlying causes of the disease. Asthma initiation and progression depends on the T helper (Th) 2 type immune response carried out by a complex interplay of cytokines, such as interleukin (IL) 4, IL5, and IL13, and the signal transducer and activator of transcription 6...
2018: Drug Design, Development and Therapy
Yong-Dong Lin, Xing-Liang Fan, Hong Zhang, Shu-Bin Fang, Cheng-Lin Li, Meng-Xia Deng, Zi-Li Qin, Ya-Qi Peng, Hong-Yu Zhang, Qing-Ling Fu
BACKGROUND: Asthma is affecting more than 300 million people worldwide, which represents the most common chronic disease among children. We previously found that mesenchymal stem cells (MSCs) derived from induced pluripotent stem cells (iPSCs) modulated the immune response on Th2-mediated asthma in vivo and in vitro. This study further evaluated the immunomodulatory effects of MSCs from human embryonic stem cells (hESCs) on asthma. METHODS: Multipotent hESC-MSCs were obtained using a feeder-free method...
January 31, 2018: Molecular Immunology
Everett K Henry, Juan M Inclan-Rico, Mark C Siracusa
Purpose of Review: It is well established that T helper type 2 (TH 2) immune responses are necessary to provide protection against helminth parasites but also to promote the detrimental inflammation associated with allergies and asthma. Given the importance of type 2 immunity and inflammation, many studies have focused on better understanding the factors that regulate TH 2 cell development and activation. As a result, significant progress has been made in understanding the signaling pathways and molecular events necessary to promote TH 2 cell polarization...
December 2017: Current Pharmacology Reports
Koichi Hirose, Takashi Ito, Hiroshi Nakajima
Asthma is a chronic inflammatory disease of the airways that is characterized by eosinophilic inflammation, mucus hypersecretion and airway remodeling that leads to airway obstruction. Although these pathognomonic features of asthma are primarily mediated by allergen-specific T helper type 2 cells (Th2 cells) and their cytokines, recent studies have revealed critical roles of lung epithelial cells in the pathogenesis of asthma. Lung epithelial cells not only form physical barriers by covering the surfaces of the airways but also sense inhaled allergens and initiate communication between the environment and the immune system...
January 31, 2018: International Immunology
Maili Lehto, Henrik Wolff, Reko Leino, Harri Alenius, Johannes Savolainen
BACKGROUND: Allergen specific immunotherapy (SIT) effectively alleviates type I allergic diseases characterized by T helper (Th) 2-type immunity. Our recent studies have shown that a synthetic trivalent glycocluster, triacedimannose (TADM), suppresses the Th2-type allergic inflammation. The aim of this study was to compare TADM with two well-known adjuvants, unmethylated cytocine-phosphate-guanine oligodeoxynucleotide (CpG) and monophosphoryl lipid A (MPLA) in a grass allergen induced chronic allergic inflammation model in mice...
January 26, 2018: Allergy
Rui Lin, Yeon Ho Choi, David A Zidar, Julia K L Walker
Allergic asthma is a complex inflammatory disease that leads to significant healthcare costs and reduction in quality of life. Although many cell types are implicated in the pathogenesis of asthma, CD4+ T helper type 2 cells (Th2) are centrally involved. We previously reported that the asthma phenotype is virtually absent in ovalbumin-sensitized and -challenged mice that lack global expression of βarrestin-2 and that CD4+ T cells from these mice displayed significantly reduced C-C motif chemokine 22 (CCL22)-mediated chemotaxis...
January 23, 2018: American Journal of Respiratory Cell and Molecular Biology
Steven F Weinstein, Rohit Katial, Shyamalie Jayawardena, Gianluca Pirozzi, Heribert Staudinger, Laurent Eckert, Vijay N Joish, Nikhil Amin, Jaman Maroni, Paul Rowe, Neil M H Graham, Ariel Teper
BACKGROUND: Dupilumab, an anti-IL-4Rα monoclonal antibody, inhibits IL-4/IL-13 signaling, key drivers of type 2/Th2 immune diseases (e.g. atopic/allergic disease). In a pivotal, phase 2b study (NCT01854047), dupilumab reduced severe exacerbations, improved lung function and quality of life, and was generally well tolerated in patients with uncontrolled persistent asthma despite using medium-to-high-dose inhaled corticosteroids plus long-acting β2-agonists. OBJECTIVE: To examine dupilumab's effect on the 22-item Sino-Nasal Outcome Test (SNOT-22) total score and its allergic rhinitis (AR)-associated items in asthma patients with comorbid perennial allergic rhinitis (PAR)...
January 17, 2018: Journal of Allergy and Clinical Immunology
Natalie Eva Nieuwenhuizen, Frank Kirstein, Jennifer Claire Hoving, Frank Brombacher
The precise mechanisms leading to development of T helper type (Th)2-driven allergic responses are unknown. We aimed to determine how IL-4 receptor alpha (IL-4Rα) signaling on CD11c+ cells influences allergen-induced Th2 responses in mice. CD11ccreIL-4Rα-/l°x mice, deficient in IL-4Rα on dendritic cells and alveolar macrophages, were compared to IL-4Rα-/l°x littermate controls in models of allergic airway disease induced by OVA/alum, OVA alone or house dust mite. Cytokine responses, eosinophil and neutrophil infiltration into the lungs, airway hyperreactivity and mucus hypersecretion were evaluated after allergen challenge...
January 17, 2018: Scientific Reports
Catherine Flanigan, Aziz Sheikh, Audrey DunnGalvin, Bronwyn K Brew, Catarina Almqvist, Bright I Nwaru
BACKGROUND: Prenatal maternal stress may influence offspring's atopic risk through sustained cortisol secretion resulting from activation of the hypothalamic-pituitary-axis (HPA), leading to Th2-biased cell differentiation in the fetus. We undertook a systematic review and meta-analysis investigating the relationship between prenatal maternal psychosocial stress and risk of asthma and allergy in the offspring. METHODS: We searched 11 electronic databases from 1960 to 2016, search the grey literature, and contacted experts in the field...
January 13, 2018: Clinical and Experimental Allergy: Journal of the British Society for Allergy and Clinical Immunology
N Mgaloblishvili, M Gotua
Asthma is a pathologically heterogeneous disease, consisting of several phenotypes. Different types of airway inflammation are the cornerstone feature of this condition. Fraction of nitric oxide in exhaled air (FENO) has been proposed as a noninvasive, specific biomarker for eosinophilic airway inflammation and has been shown to be elevated in patients with allergic asthma phenotype. More recent studies indicate that FeNO identifies T-helper cell type 2 (Th2)-mediated airway inflammation with a high predictive value for identifying inhaled corticosteroid (ICS) responsive airway inflammation...
December 2017: Georgian Medical News
Momoko Kitaoka, Ayaka Naritomi, Yoshinori Kawabe, Masamichi Kamihira, Noriho Kamiya, Masahiro Goto
Antigen-specific immunotherapy is the only curative approach for the treatment of allergic diseases such as Japanese cedar pollinosis. Immunotherapy using a T cell epitope vaccine in combination with the adjuvant R848 is of particular interest as a safe and effective approach to treat allergic diseases. Herein, we propose a simple and easy to handle vaccine administration method using the original solid-in-oil (S/O) nanodispersion system that permeates through the skin. The S/O nanodispersion system is composed of nanoparticles of hydrophilic molecules surrounded with hydrophobic surfactants that are dispersed in an oil vehicle...
March 2017: Bioengineering & Translational Medicine
Yiling Zhang, Ying Feng, Liang Li, Xianmiao Ye, Jinlin Wang, Qian Wang, Pingchao Li, Na Li, Xuehua Zheng, Xiang Gao, Chufang Li, Feng Li, Baoqing Sun, Kefang Lai, Zhong Su, Nanshan Zhong, Ling Chen, Liqiang Feng
Current treatments for allergic asthma primarily ameliorate symptoms rather than inhibit disease progression. Regulating the excessive T helper type 2 (Th2) responses may prevent asthma exacerbation. In this study, we investigated the protective effects of Ad5-gsgAM, an adenovirus vector carrying two mycobacterial antigens Ag85A and Mtb32, against allergic asthma. Using an ovalbumin (OVA)-induced asthmatic mouse model, we found that Ad5-gsgAM elicited much more Th1-biased CD4+ T and CD8+ T cells than bacillus Calmette-Guérin (BCG)...
January 4, 2018: Journal of Molecular Medicine: Official Organ of the "Gesellschaft Deutscher Naturforscher und Ärzte"
Amarjit Mishra, Xianglan Yao, Ankit Saxena, Elizabeth M Gordon, Maryann Kaler, Rosemarie A Cuento, Amisha V Barochia, Pradeep K Dagur, J Philip McCoy, Karen J Keeran, Kenneth R Jeffries, Xuan Qu, Zu-Xi Yu, Stewart J Levine
BACKGROUND: The LDL-receptor related protein 1 (LRP-1) is a scavenger receptor that regulates adaptive immunity and inflammation. LRP-1 is not known to modulate the pathogenesis of allergic asthma. OBJECTIVE: To assess whether LRP-1 expression by dendritic cells (DCs) modulates adaptive immune responses in house dust mite (HDM)-induced airways disease. METHODS: LRP-1 expression on peripheral blood DCs was quantified by flow cytometry. The role of LRP-1 in modulating HDM-induced airways disease was assessed in mice with a deletion of LRP-1 in CD11c+ cells (Lrp1fl/fl; CD11c-Cre) and by the adoptive transfer of HDM-pulsed CD11b+ DCs from Lrp1fl/fl; CD11c-Cre mice to wild-type mice...
December 20, 2017: Journal of Allergy and Clinical Immunology
Benjamin F Sallis, Lena Erkert, Sherezade Moñino-Romero, Utkucan Acar, Rina Wu, Liza Konnikova, Willem S Lexmond, Matthew J Hamilton, W Augustine Dunn, Zsolt Szepfalusi, Jon A Vanderhoof, Scott B Snapper, Jerrold R Turner, Jeffrey D Goldsmith, Lisa A Spencer, Samuel Nurko, Edda Fiebiger
BACKGROUND: Diagnostic evaluation of eosinophilic esophagitis (EoE) remains difficult, particularly the assessment of the patient's allergic status. OBJECTIVE: Establish an automated medical algorithm to assist in the evaluation of EoE. METHODS: Machine learning techniques were used to establish a diagnostic probability score for EoE (pEoE) based on esophageal mRNA transcript patterns from biopsies of patients with EoE, gastroesophageal reflux disease, and controls...
December 19, 2017: Journal of Allergy and Clinical Immunology
Tomoya Miura, Atsushi Matsubara, Naomi Kudo, Ryutaro Hara, Junko Takahata, Akira Sasaki
OBJECTIVE: In the present study, we aimed to clarify the expression of thymic stromal lymphopoietin (TSLP), a key trigger of Th2-type allergic disease, in the middle ear mucosa of eosinophilic otitis media (EOM). METHODS: An immunohistological study of TSLP was conducted in patients with EOM and in animal models of EOM constructed by intraperitoneal and intratympanic injection of ovalbumin for 7 and 14 days. In addition, the messenger RNA (mRNA) expression of TSLP in the middle ear mucosa of the animal models was analyzed using real-time PCR, and was compared with that of the control animals...
December 22, 2017: Acta Oto-laryngologica
Corinne Cayrol, Jean-Philippe Girard
Interleukin-33 (IL-33) is a tissue-derived nuclear cytokine from the IL-1 family abundantly expressed in endothelial cells, epithelial cells and fibroblast-like cells, both during homeostasis and inflammation. It functions as an alarm signal (alarmin) released upon cell injury or tissue damage to alert immune cells expressing the ST2 receptor (IL-1RL1). The major targets of IL-33 in vivo are tissue-resident immune cells such as mast cells, group 2 innate lymphoid cells (ILC2s) and regulatory T cells (Tregs)...
January 2018: Immunological Reviews
Hans O Kalkman, Dominik Feuerbach
Atopic diseases are frequently co-morbid with autism spectrum disorders (ASD). Allergic responses are associated with an activation of mast cells, innate lymphoid cells, and Th2 cells. These cells produce type-2 cytokines (IL4 and IL13), which stimulate microglia and macrophages to adopt a phenotype referred to as 'alternative activation' or 'M2A'. M2A-polarized macrophages and microglia play a physiological role in tissue repair by secreting growth factors such as brain-derived neurotrophic factor (BDNF) and insulin-like growth factor-1...
December 9, 2017: Pharmaceuticals
Mohamed H Shamji, Stephen R Durham
Allergen immunotherapy is effective in patients with IgE-dependent allergic rhinitis and asthma. When immunotherapy is given continuously for 3 years, there is persistent clinical benefit for several years after its discontinuation. This disease-modifying effect is both antigen-specific and antigen-driven. Clinical improvement is accompanied by decreases in numbers of effector cells in target organs, including mast cells, basophils, eosinophils, and type 2 innate lymphoid cells. Immunotherapy results in the production of blocking IgG/IgG4 antibodies that can inhibit IgE-dependent activation mediated through both high-affinity IgE receptors (FcεRI) on mast cells and basophils and low-affinity IgE receptors (FcεRII) on B cells...
December 2017: Journal of Allergy and Clinical Immunology
Goro Matsuzaki, Masayuki Umemura
Interleukin-17 family cytokines, consisting of six members, participate in immune response in infections and autoimmune and inflammatory diseases. The prototype cytokine of the family, IL-17A, was originally identified from CD4+ T cells which are now termed Th17 cells. Later, IL-17A-producing cells were expanded to include various hematopoietic cells, namely CD8+ T cells (Tc17), invariant NKT cells, γδ T cells, non-T non-B lymphocytes (termed type 3 innate lymphoid cells) and neutrophils. Some IL-17 family cytokines other than IL-17A are also expressed by CD4+ T cells: IL-17E by Th2 cells and IL-17F by Th17 cells...
January 2018: Microbiology and Immunology
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