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Th2- type allergic diseases

Lauriane Galle-Treger, Yuzo Suzuki, Nisheel Patel, Ishwarya Sankaranarayanan, Jennifer L Aron, Hadi Maazi, Lin Chen, Omid Akbari
Allergic asthma is a complex and chronic inflammatory disorder that is associated with airway hyperreactivity (AHR) and driven by Th2 cytokine secretion. Type 2 innate lymphoid cells (ILC2s) produce large amounts of Th2 cytokines and contribute to the development of AHR. Here, we show that ILC2s express the α7-nicotinic acetylcholine receptor (α7nAChR), which is thought to have an anti-inflammatory role in several inflammatory diseases. We show that engagement of a specific agonist with α7nAChR on ILC2s reduces ILC2 effector function and represses ILC2-dependent AHR, while decreasing expression of ILC2 key transcription factor GATA-3 and critical inflammatory modulator NF-κB, and reducing phosphorylation of upstream kinase IKKα/β...
October 18, 2016: Nature Communications
Masafumi Moriyama, Seiji Nakamura
IgG4-related disease (IgG4-RD) is a systemic disease characterized by elevated serum IgG4 levels and a strong infiltration of IgG4-positive plasma cells in various organs. IgG4-RD patients also frequently suffer from allergic diseases, including asthma and atopic dermatitis. It is well known that T helper type 2 (Th2) cells have an important role in the initiation of allergic diseases, and Th2 cytokines such as interleukin (IL)-4 and IL-13 promote class switching to IgG4. Therefore, IgG4-RD is considered to be a Th2-predominant disease...
October 16, 2016: Current Topics in Microbiology and Immunology
Michele Miraglia Del Giudice, Annalisa Allegorico
The role of vitamin D in calcium and phosphate homeostasis is well known; however, in addition to traditional functions, vitamin D modulates a variety of processes, and evidence shows that it has an important role in different allergic diseases such as asthma, atopic dermatitis, and food allergy. Vitamin D acts by binding to the vitamin D receptor, which is present in a variety of tissues; for this reason it is considered a hormone. One of the most important functions is to modulate the immune system response, both innate and adaptive, by suppressing Th2-type response and increasing natural killer cells...
November 2016: Journal of Clinical Gastroenterology
Shan-Shan Meng, Rong Gao, Bing-di Yan, Jin Ren, Fei Wu, Peng Chen, Jie Zhang, Li-Fang Wang, Yuan-Ming Xiao, Jing Liu
BACKGROUND: Maternal allergic disease history and impaired regulatory T-cells (Tregs) are critical risk factors for allergy development in children. However, the mechanisms that underlie these risk factors remain poorly defined. Therefore, the aim of this study was to assess whether maternal allergies affect the Tregs of offspring and lead to allergy development in childhood. METHODS: A total of 332 mothers of healthy newborns (234 from no allergic mothers, 98 from allergic mothers) were recruited to this study...
2016: Respiratory Research
Yun Liang, Johann E Gudjonsson
Dysregulation of the type 2 immune system presents with various manifestations, including allergic inflammation, and has emerged as an alarming public health issue. The pathological mechanisms that underlie T helper type 2 cell-driven (Th2-driven) allergic diseases remain unclear. In particular, it is not completely understood how type 2 immunity is restricted in inflammatory responses. In this issue of the JCI, Lexmond et al. use Wiskott-Aldrich syndrome as a model disease and establish that the Wiskott-Aldrich gene product (WASP) serves an essential role in T regulatory cells to contain Th2 effector cell differentiation and prevent allergic sensitization to dietary antigens...
October 3, 2016: Journal of Clinical Investigation
Cristina Ghirelli, Benjamin Sadacca, Fabien Reyal, Raphaël Zollinger, Paula Michea, Philémon Sirven, Lucia Pattarini, Carolina Martínez-Cingolani, Maude Guillot-Delost, André Nicolas, Alix Scholer-Dahirel, Vassili Soumelis
Thymic stromal lymphopoietin (TSLP) is an epithelial cell-derived cytokine that primes dendritic cells for Th2 induction. It has been implicated in different types of allergic diseases. Recent work suggested that TSLP could play an important role in the tumor microenvironment and influence tumor progression, in particular in breast cancer. In this study we systematically assessed the production of TSLP at the mRNA and protein levels in several human breast cancer cell lines, large-scale public transcriptomics data sets, and primary human breast tumors...
August 2016: Oncoimmunology
Hern-Tze Tina Tan, Kazunari Sugita, Cezmi A Akdis
PURPOSE OF REVIEW: The development of biological therapies has rapidly progressed during the last few years, and major advances were reported for the treatment of allergic diseases, such as atopic dermatitis, allergic rhinitis, urticaria, food allergy, and asthma. Here, we review biologicals targeting the type 2 immune response involving Th2 cells, type 2 innate lymphoid cells, natural killer T cells, mast cells, basophils, and epithelial cells, such as IL-4, IL-5, IL-13, IL-31, tumor necrosis factor alpha (TNF-α), and thymic stromal lymphopoietin (TSLP)...
October 2016: Current Allergy and Asthma Reports
Byung-Seok Kim, Young-Jun Park, Yeonseok Chung
The discovery of two distinct subsets of helper T cells, IFN-γ-producing Th1 cells and IL-4-producing Th2 cells, about three decades ago enabled us to understand the immunopathology of cell-mediated and allergic inflammatory diseases in humans. The observation that T cell-mediated experimental autoimmune diseases can be induced in mice lacking Th1 and Th2 cell responses prompted many immunologists to hypothesize that there might be additional subsets in helper T cell population which mediate autoimmunity in the absence of Th1 and Th2 cells...
August 30, 2016: Archives of Pharmacal Research
Nicole Schütze, Stefanie Trojandt, Stephanie Kuhn, Janina M Tomm, Martin von Bergen, Jan C Simon, Tobias Polte
IL-9-secreting Th9 cells have been considered to play a pivotal role in the pathogenesis of atopic diseases. To what extent IL-9-producing cells are induced or regulated by sensitization with naturally occurring allergens is not yet clear. Naturally occurring allergens are capable of inducing IL-6 production in dendritic cells (DCs). Whether allergen-induced IL-6 supports a Th9 subtype by increasing IL-9 production, as observed in in vitro studies, or rather favors Th17 differentiation is not finally resolved...
October 1, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
Hirofumi Tsuzuki, Yojiro Arinobu, Kohta Miyawaki, Ayako Takaki, Shun-Ichiro Ota, Yuri Ota, Hiroki Mitoma, Mitsuteru Akahoshi, Yasuo Mori, Hiromi Iwasaki, Hiroaki Niiro, Hiroshi Tsukamoto, Koichi Akashi
Interleukin-33 (IL-33) induces Th2 cytokine production and eosinophilia independently of acquired immunity, leading to innate immunity-mediated allergic inflammation. Allergy-related innate myeloid cells such as eosinophils, basophils and mast cells express the IL-33 receptor (IL-33R), but it is still unknown how IL-33 regulates allergic inflammation involving these cells and their progenitors. Here, we revealed that the functional IL-33R was expressed on eosinophil progenitors (EoPs), basophil progenitors (BaPs) and mast cell progenitors (MCPs)...
August 29, 2016: Immunology
Handong Zheng, Xing Zhang, Eliseo F Castillo, Yan Luo, Meilian Liu, Xuexian O Yang
Allergic asthma and obesity are the leading health problems in the world. Many studies have shown that obesity is a risk factor of development of asthma. However, the underlying mechanism has not been well established. In this study, we demonstrate that leptin, an adipokine elevated in obese individuals, promoted proliferation and survival of pro-allergic type 2 helper T cells and group 2 innate lymphoid cells and production of type 2 cytokines, which together contribute to allergic responses. Leptin activates mTORC1, MAPK, and STAT3 pathways in TH2 cells...
October 14, 2016: Journal of Biological Chemistry
Wael N Sayej, Antoine Ménoret, Anu S Maharjan, Marina Fernandez, Zhu Wang, Fabiola Balarezo, Jeffrey S Hyams, Francisco A Sylvester, Anthony T Vella
Eosinophilic esophagitis (EoE) is an emerging allergic, IgE- and non-IgE (Th2 cell)-mediated disease. There are major gaps in the understanding of the basic mechanisms that drive the persistence of EoE. We investigated whether esophageal biopsies from children with EoE demonstrate an inflammatory response that is distinct from normal controls. We prospectively enrolled 84 patients, of whom 77 were included in our analysis, aged 4-17 years (12.8±3.8 years; 81% males). Five esophageal biopsies were collected from each patient at the time of endoscopy...
July 2016: Clinical & Translational Immunology
Sarita Sehra, Purna Krishnamurthy, Byunghee Koh, Hong-Ming Zhou, Lee Seymour, Nahid Akhtar, Jeffrey B Travers, Matthew J Turner, Mark H Kaplan
Atopic dermatitis (AD) is a chronic inflammatory skin disease induced by a complex interaction between susceptibility genes encoding skin barrier components and environmental allergen exposure that results in type 2 cytokine production. Although genetic lesions in either component can be risk factors for disease in patients, whether these pathways interact in the development of AD is not clear. To test this, we mated mice with T-cell specific expression of constitutively active Stat6 (Stat6VT) that spontaneously develop allergic skin inflammation with Flaky tail (Ft) mice that have mutations in Flg and Tmem79 genes that each affect skin barrier function...
August 11, 2016: European Journal of Immunology
Nathan L Sanders, Anil Mishra
Interleukin (IL)-18 is an IL-1 family cytokine expressed by macrophages, dendritic cells, epithelial cells, and keratinocytes and is implicated in various aspects of both the innate and adaptive immune systems. IL-18 signals similar to IL-1β intracellularly to activate gene transcription. Since its discovery, IL-18 has been demonstrated to play a key role in pathogen defense from helminths and some bacteria. Recently however, evidence has accumulated that IL-18 expression is increased in many presentations of allergic disease...
July 15, 2016: Cytokine & Growth Factor Reviews
Chang-Ching Wei, Cheng-Li Lin, Te-Chun Shen, Jeng-Dau Tsai
Primary immune thrombocytopenia (ITP) is currently defined as an acquired autoimmune disorder with persistent thrombocytopenia. However, the temporal interaction between T helper type 2 cell (Th2)-mediated allergic diseases and T helper type 1 cell (Th1)-mediated ITP remains unknown. Atopic dermatitis (AD) is considered one of the first steps in the atopic march. Herein, we conducted a population-based cohort analysis to investigate the risk of ITP in children with AD in comparison with non-AD controls. We subsequently compared the occurrence of other autoimmune diseases in ITP children in both AD and non-AD cohorts...
July 2016: Medicine (Baltimore)
Josipa Raguz, Ines Jeric, Theodora Niault, Joanna Daniela Nowacka, Sanya Eduarda Kuzet, Christian Rupp, Irmgard Fischer, Silvia Biggi, Tiziana Borsello, Manuela Baccarini
The RAS pathway is central to epidermal homeostasis, and its activation in tumors or in Rasopathies correlates with hyperproliferation. Downstream of RAS, RAF kinases are actionable targets regulating keratinocyte turnover; however, chemical RAF inhibitors paradoxically activate the pathway, promoting epidermal proliferation. We generated mice with compound epidermis-restricted BRAF/RAF1 ablation. In these animals, transient barrier defects and production of chemokines and Th2-type cytokines by keratinocytes cause a disease akin to human atopic dermatitis, characterized by IgE responses and local and systemic inflammation...
2016: ELife
Naruhito Iwasaki, Kazufumi Matsushita, Ayumi Fukuoka, Masakiyo Nakahira, Makoto Matsumoto, Shoko Akasaki, Koubun Yasuda, Takeshi Shimizu, Tomohiro Yoshimoto
BACKGROUND: Allergen-mediated cross-linking of IgE on mast cells/basophils is a well-recognized trigger for type 1 allergic diseases such as allergic rhinitis (AR). However, allergens may not be the sole trigger for AR, and several allergic-like reactions are induced by non-IgE-mediated mechanisms. OBJECTIVE: We sought to describe a novel non-IgE-mediated, endotoxin-triggered nasal type-1-hypersensitivity-like reaction in mice. METHODS: To investigate whether endotoxin affects sneezing responses, mice were intraperitoneally immunized with ovalbumin (OVA), then nasally challenged with endotoxin-free or endotoxin-containing OVA...
May 24, 2016: Journal of Allergy and Clinical Immunology
Preeti Bansal, Shailendera Nath Gaur, Naveen Arora
Phospholipase A2 (sPLA2), pivotal for allergic and inflammatory response, hydrolyses phosphatidylcholine (PC) to lysophosphatidylcholine (LPC). In present study, the role of LPC in allergic airway disease manifestation was studied using mouse model. Balb/c mice were immunized using cockroach extract (CE) and LPC release was blocked by sPLA2 inhibitor. Airway hyperresponse (AHR), lung-histology, total and differential leukocyte count (TLC&DLC), Th2 type cytokines, sPLA2 activity and LPC levels in bronchoalveolar lavage fluid (BALF) were measured...
2016: Scientific Reports
Grégory Seumois, Jose Zapardiel-Gonzalo, Brandie White, Divya Singh, Veronique Schulten, Myles Dillon, Denize Hinz, David H Broide, Alessandro Sette, Bjoern Peters, Pandurangan Vijayanand
Allergic asthma and rhinitis are two common chronic allergic diseases that affect the lungs and nose, respectively. Both diseases share clinical and pathological features characteristic of excessive allergen-induced type 2 inflammation, orchestrated by memory CD4(+) T cells that produce type 2 cytokines (Th2 cells). However, a large majority of subjects with allergic rhinitis do not develop asthma, suggesting divergence in disease mechanisms. Because Th2 cells play a pathogenic role in both these diseases and are also present in healthy nonallergic subjects, we performed global transcriptional profiling to determine whether there are qualitative differences in Th2 cells from subjects with allergic asthma, rhinitis, and healthy controls...
July 15, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
Nicholas Venturelli, Willem S Lexmond, Asa Ohsaki, Samuel Nurko, Hajime Karasuyama, Edda Fiebiger, Michiko K Oyoshi
BACKGROUND: Eosinophilic esophagitis (EoE) is an allergic inflammatory disorder characterized by accumulation of eosinophils in the esophagus. EoE often coexists with atopic dermatitis, a chronic inflammatory skin disease. The impaired skin barrier in patients with atopic dermatitis has been suggested as an entry point for allergic sensitization that triggers development of EoE. OBJECTIVE: We sought to define the mechanisms whereby epicutaneous sensitization through a disrupted skin barrier induces development of EoE...
April 19, 2016: Journal of Allergy and Clinical Immunology
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