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Th17 IgE

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https://www.readbyqxmd.com/read/28442583/seletalisib-characterization-of-a-novel-potent-and-selective-inhibitor-of-pi3k%C3%AE
#1
Rodger A Allen, Daniel C Brookings, Mark J Powell, Jean Delgado, Lindsay K Shuttleworth, Mark Merriman, Ian J Fahy, Roohi Tewari, John P Silva, Louise J Healy, Gareth C G Davie, Breda Twomey, Rona M Cutler, Apoorva Kotian, Andrea Crosby, Gillian McCluskey, Gillian Watt, Andrew Payne
PI3Ks are key signaling enzymes regulating cellular survival, development and function. Expression of the PI3Kδ isoform is largely restricted to leukocytes and it plays a key role in immune cell development and function. Seletalisib is a novel small molecule inhibitor of PI3Kδ that was evaluated in biochemical assays, cellular assays of adaptive and innate immunity, and an in vivo rat model of inflammation. Our findings show that seletalisib is a potent, ATP-competitive and highly selective PI3Kδ inhibitor able to block AKT phosphorylation following activation of the BCR in a B-cell line...
April 25, 2017: Journal of Pharmacology and Experimental Therapeutics
https://www.readbyqxmd.com/read/28430123/functional-analysis-of-the-rs774872314-rs116171003-rs200231898-and-rs201107751-polymorphisms-in-the-human-ror%C3%AE-t-gene-promoter-region
#2
Marcin Ratajewski, Marcin Słomka, Kaja Karaś, Marta Sobalska-Kwapis, Małgorzata Korycka-Machała, Anna Sałkowska, Jarosław Dziadek, Dominik Strapagiel, Jarosław Dastych
RAR-related orphan receptor gamma RORγT, a tissue-specific isoform of the RORC gene, plays a critical role in the development of naive CD4+ cells into fully differentiated Th17 lymphocytes. Th17 lymphocytes are part of the host defense against numerous pathogens and are also involved in the pathogenesis of inflammatory diseases, including autoimmune disorders. In this study, we functionally examined four naturally occurring polymorphisms located within one of the previously identified GC-boxes in the promoter region of the gene...
April 21, 2017: Genes
https://www.readbyqxmd.com/read/28428203/tslp-activated-dendritic-cells-induce-human-t-follicular-helper-cell-differentiation-through-ox40-ligand
#3
Lucia Pattarini, Coline Trichot, Sofia Bogiatzi, Maximilien Grandclaudon, Stephan Meller, Zela Keuylian, Melanie Durand, Elisabetta Volpe, Stefania Madonna, Andrea Cavani, Andrea Chiricozzi, Marco Romanelli, Toshiyuki Hori, Alain Hovnanian, Bernhard Homey, Vassili Soumelis
T follicular helper cells (Tfh) are important regulators of humoral responses. Human Tfh polarization pathways have been thus far associated with Th1 and Th17 polarization pathways. How human Tfh cells differentiate in Th2-skewed environments is unknown. We show that thymic stromal lymphopoietin (TSLP)-activated dendritic cells (DCs) promote human Tfh differentiation from naive CD4 T cells. We identified a novel population, distinct from Th2 cells, expressing IL-21 and TNF, suggestive of inflammatory cells...
April 20, 2017: Journal of Experimental Medicine
https://www.readbyqxmd.com/read/28423590/neutralization-of-interleukin-17-suppresses-allergic-rhinitis-symptoms-by-downregulating-th2-and-th17-responses-and-upregulating-the-treg-response
#4
Zhao Wei Gu, Yun Xiu Wang, Zhi Wei Cao
Allergic rhinitis (AR) has long been considered to predominantly involve the actions of Th2 cells, with relatively small contributions from Th1 cells. In recent years, the discovery of Th17 and regulatory T (Treg) cells has rendered the Th1/Th2 balance paradigm more complex and expanded our understanding of the pathogenesis of AR. IL-17, a key cytokine produced by Th17 cells, is known to induce allergen-specific Th2 cell activation, eosinophil and neutrophil accumulation, and serum IgE production in asthma; all of these features may play important roles in AR...
April 4, 2017: Oncotarget
https://www.readbyqxmd.com/read/28423239/a-novel-jak-inhibitor-jte-052-reduces-skin-inflammation-and-ameliorates-chronic-dermatitis-in-rodent-models-comparison-with-conventional-therapeutic-agents
#5
Atsuo Tanimoto, Yuichi Shinozaki, Yasuo Yamamoto, Yoshiaki Katsuda, Eriko Riya, Kaoru Toyoda, Kochi Kakimoto, Yukari Kimoto, Wataru Amano, Noriko Konishi, Mikio Hayashi
Janus kinases (JAKs) are required for several inflammatory cytokine signaling pathways and are implicated in the pathogenesis of chronic dermatitis, including atopic dermatitis and psoriasis. JAK inhibitors are therefore promising therapeutic candidates for chronic dermatitis. In this study, we evaluated the effects of the novel JAK inhibitor JTE-052 on inflammatory responses associated with chronic dermatitis, and compared its profile with those of conventional therapeutic agents in rodent models of chronic dermatitis...
April 19, 2017: Experimental Dermatology
https://www.readbyqxmd.com/read/28396669/basophil-activation-dependent-autoantibody-and-interleukin-17-production-exacerbate-systemic-lupus-erythematosus
#6
Qingjun Pan, Li Gong, Haiyan Xiao, Yongmin Feng, Lu Li, Zhenzhen Deng, Ling Ye, Jian Zheng, Carol A Dickerson, Lin Ye, Ning An, Chen Yang, Hua-Feng Liu
OBJECTIVE: Autoantibody and inflammatory cytokines play crucial roles in the development of systemic lupus erythematosus (SLE); however, the regulation of their production warrants further investigation. This study aimed to investigate the role of basophil activation in the development of SLE based on studies in patients with SLE and spontaneous lupus-prone MRL-lpr/lpr mice. METHODS: The phenotypes of peripheral basophils and the production of autoantibody and interleukin (IL)-17 in patients with SLE were determined by flow cytometry and enzyme-linked immunosorbent assay, and also their correlations were investigated by statistical analysis...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28293930/anti-interleukin-9-antibody-increases-the-effect-of-allergen-specific-immunotherapy-in-murine-allergic-rhinitis
#7
Ji Hyeon Shin, Do Hyun Kim, Boo Young Kim, Sung Won Kim, Se Hwan Hwang, Joohyung Lee, Soo Whan Kim
PURPOSE: Interleukin (IL)-9 induces allergic responses; however, the roles of anti-IL-9 antibody in the induction of tolerance remain unclear. This study investigated the effects of anti-IL-9 antibody on oral tolerance (OT) in a mouse model of allergic rhinitis (AR). METHODS: BALB/c mice were divided into 4 groups: the control, AR, OT, and OT with anti-IL-9 antibody (OT+IL9AB) groups. Ovalbumin (OVA) was used for sensitization and challenge. Mice in the OT and OT+IL9AB groups were fed OVA for immunotherapy...
May 2017: Allergy, Asthma & Immunology Research
https://www.readbyqxmd.com/read/28263381/obesity-promotes-prolonged-ovalbumin-induced-airway-inflammation-modulating-t-helper-type-1-th1-th2-and-th17-immune-responses-in-balb-c-mice
#8
F M C Silva, E E Oliveira, A C C Gouveia, A S S Brugiolo, C C Alves, J O A Correa, J Gameiro, J Mattes, H C Teixeira, A P Ferreira
Clinical and epidemiological studies indicate that obesity affects the development and phenotype of asthma by inducing inflammatory mechanisms in addition to eosinophilic inflammation. The aim of this study was to assess the effect of obesity on allergic airway inflammation and T helper type 2 (Th2) immune responses using an experimental model of asthma in BALB/c mice. Mice fed a high-fat diet (HFD) for 10 weeks were sensitized and challenged with ovalbumin (OVA), and analyses were performed at 24 and 48 h after the last OVA challenge...
March 6, 2017: Clinical and Experimental Immunology
https://www.readbyqxmd.com/read/28134325/basophil-derived-il-6-regulates-th17-cell-differentiation-and-cd4-t-cell-immunity
#9
Chae Min Yuk, Hyeung Ju Park, Bo-In Kwon, Sang Joon Lah, Jun Chang, Ji-Young Kim, Kyung-Mi Lee, Su-Hyung Park, Seokchan Hong, Seung-Hyo Lee
Basophils are rare, circulating granulocytes proposed to be involved in T helper (TH) type 2 immunity, mainly through secretion of interleukin (IL)-4. In addition to IL-4, basophils produce IL-6 and tumor necrosis factor (TNF)-α in response to immunoglobulin E (IgE) crosslinking. Differentiation of TH17 cells requires IL-6 and transforming growth factor (TGF)-β, but whether basophils play a significant role in TH17 induction is unknown. Here we show a role for basophils in TH17 cell development by using in vitro T cell differentiation and in vivo TH17-mediated inflammation models...
January 30, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28117118/intranasal-azelastine-and-mometasone-exhibit-a-synergistic-effect-on-a-murine-model-of-allergic-rhinitis
#10
Do Hyun Kim, Boo-Young Kim, Ji-Hyeon Shin, Sung Won Kim, Soo Whan Kim
PURPOSE: The purpose of this study was to compare the anti-allergic effects of the combination of azelastine and mometasone with those of either agent alone in a Dermatophagoides farinae (Derf)-induced murine model of allergic rhinitis (AR). MATERIALS AND METHODS: Forty BALB/c mice were divided into five groups: azelastine (A), mometasone (M), a combination of azelastine and mometasone (MA), Derf, and control. Derf served as the allergen. Allergic symptom scores, eosinophil counts, and serum Derf-specific IgE levels were measured...
March 2017: American Journal of Otolaryngology
https://www.readbyqxmd.com/read/28063040/a-mouse-model-for-atopic-dermatitis-using-topical-application-of-vitamin-d3-or-of-its-analog-mc903
#11
Verena Moosbrugger-Martinz, Matthias Schmuth, Sandrine Dubrac
Atopic dermatitis (AD) is a chronic relapsing inflammatory skin disease with pruritus and high prevalence. Indeed, 15-30 % of children and 2-10 % of adults from industrialized countries are affected. Acute AD lesions are characterized by epidermal hyperplasia associated with a dominant Th2/Th17 immune response and dermal inflammatory infiltrates. Moreover, the expression of alarmins such as TSLP, IL-33, and IL-25 is upregulated in acute AD lesions. Topical application of vitamin D3 or of its low-calcemic analog MC903 induces changes in skin morphology and inflammation resembling immune perturbations observed in acute lesions of patients with AD...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/27858144/th9-and-other-il-9-producing-cells-in-allergic-asthma
#12
REVIEW
Sonja Koch, Nina Sopel, Susetta Finotto
Allergic asthma is a worldwide increasing chronic disease of the airways which affects more than 300 million people. It is associated with increased IgE, mast cell activation, airway hyperresponsiveness (AHR), mucus overproduction and remodeling of the airways. Previously, this pathological trait has been associated with T helper type 2 (Th2) cells. Recently, different CD4(+) T cell subsets (Th17, Th9) as well as cells of innate immunity, like mast cells and innate lymphoid cells type 2 (ILC2s), which are all capable of producing the rediscovered cytokine IL-9, are known to contribute to this disease...
November 17, 2016: Seminars in Immunopathology
https://www.readbyqxmd.com/read/27643438/foxp3-tregs-require-wasp-to-restrain-th2-mediated-food-allergy
#13
Willem S Lexmond, Jeremy A Goettel, Jonathan J Lyons, Justin Jacobse, Marion M Deken, Monica G Lawrence, Thomas H DiMaggio, Daniel Kotlarz, Elizabeth Garabedian, Paul Sackstein, Celeste C Nelson, Nina Jones, Kelly D Stone, Fabio Candotti, Edmond H H M Rings, Adrian J Thrasher, Joshua D Milner, Scott B Snapper, Edda Fiebiger
In addition to the infectious consequences of immunodeficiency, patients with Wiskott-Aldrich syndrome (WAS) often suffer from poorly understood exaggerated immune responses that result in autoimmunity and elevated levels of serum IgE. Here, we have shown that WAS patients and mice deficient in WAS protein (WASP) frequently develop IgE-mediated reactions to common food allergens. WASP-deficient animals displayed an adjuvant-free IgE-sensitization to chow antigens that was most pronounced for wheat and soy and occurred under specific pathogen-free as well as germ-free housing conditions...
October 3, 2016: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/27606627/immunological-profile-in-individuals-with-schistosomal-myeloradiculopathy
#14
Ramon de Almeida Kruschewsky, Luciana Santos Cardoso, Jamille Souza Fernandes, Robson da Paixão de Souza, Diego Mota Lopes, Otavio Augusto Moreno de Carvalho, Maria Ilma Araujo
BACKGROUND: Schistosomal myeloradiculopathy (SMR) is the most serious ectopic presentation of Schistosoma mansoni infection. The pathogenesis occurs mainly via the host inflammatory response to the eggs of the parasite that are stuck in the central nervous system, and the diagnosis is generally made by the exclusion of other neurological diseases. OBJECTIVE: We aimed to evaluate the immune status of SMR patients and to identify a marker for SMR diagnosis. METHODS: We enrolled 15 patients with a presumptive diagnosis of SMR, and the control groups included 17 patients with myelopathy associated with human T cell lymphotropic virus type 1 (HTLV-1) and 11 with other neurological disorders...
2016: Neuroimmunomodulation
https://www.readbyqxmd.com/read/27554822/dedicator-of-cytokinesis-8-deficient-cd4-t%C3%A2-cells-are-biased-to-a-th2-effector-fate-at-the-expense-of-th1-and-th17%C3%A2-cells
#15
Stuart G Tangye, Bethany Pillay, Katrina L Randall, Danielle T Avery, Tri Giang Phan, Paul Gray, John B Ziegler, Joanne M Smart, Jane Peake, Peter D Arkwright, Sophie Hambleton, Jordan Orange, Christopher C Goodnow, Gulbu Uzel, Jean-Laurent Casanova, Saul Oswaldo Lugo Reyes, Alexandra F Freeman, Helen C Su, Cindy S Ma
BACKGROUND: Dedicator of cytokinesis 8 (DOCK8) deficiency is a combined immunodeficiency caused by autosomal recessive loss-of-function mutations in DOCK8. This disorder is characterized by recurrent cutaneous infections, increased serum IgE levels, and severe atopic disease, including food-induced anaphylaxis. However, the contribution of defects in CD4(+) T cells to disease pathogenesis in these patients has not been thoroughly investigated. OBJECTIVE: We sought to investigate the phenotype and function of DOCK8-deficient CD4(+) T cells to determine (1) intrinsic and extrinsic CD4(+) T-cell defects and (2) how defects account for the clinical features of DOCK8 deficiency...
August 20, 2016: Journal of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/27544740/diversity-of-th-cytokine-profiles-in-patients-with-chronic-rhinosinusitis-a%C3%A2-multicenter-study-in-europe-asia-and-oceania
#16
Xiangdong Wang, Nan Zhang, Mingyu Bo Ms, Gabriele Holtappels, Ming Zheng, Hongfei Lou, Hong Wang, Luo Zhang, Claus Bachert
BACKGROUND: To date, no study has evaluated the diversity of TH cell cytokine patterns of patients with chronic rhinosinusitis (CRS) among centers in different continents using identical methods. OBJECTIVE: We sought to assess TH cytokine profiles in patients with CRS from Europe, Asia, and Australia. METHODS: Patients with chronic rhinosinusitis with nasal polyps (CRSwNP) and without nasal polyps (CRSsNP; n = 435) and control subjects (n = 138) were recruited from centers in Adelaide, Benelux, Berlin, Beijing, Chengdu, and Tochigi...
July 15, 2016: Journal of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/27510042/solanum-tuberosum-l-cv-hongyoung-extract-inhibits-2-4%C3%A2-dinitrochlorobenzene%C3%A2-induced-atopic-dermatitis-in-nc-nga-mice
#17
Myung Ah Kang, Se-Young Choung
Solanum tuberosum L. cv Hongyoung (SH) is a widely consumed anthocyanin-rich food and medicinal plant, which possesses anti‑inflammatory and anti‑allergic activities. The present study aimed to examine the inhibitory effects of SH extract on atopic dermatitis (AD)‑like skin lesions induced by the topical application of 2,4‑dinitrochlorobenzene (DNCB) in NC/Nga mice. SH extract was orally administered to the DNCB‑treated NC/Nga mice. The anti‑AD effects of SH extract were examined by measuring symptom severity; ear thickness; scratching behavior; serum levels of immunoglobulin (Ig)E; T‑helper (Th)1, Th2 and Th17 cytokine levels in the spleen; mRNA expression levels of inflammatory cytokines and chemokines; and tissue infiltration of inflammatory cells...
October 2016: Molecular Medicine Reports
https://www.readbyqxmd.com/read/27403198/effects-of-sohamhyoong-tang-on-ovalbumin-induced-allergic-reaction-in-balb-c-mice
#18
So Hyun Jo, Yun Jung Lee, Dae Gill Kang, Ho Sub Lee, Dae Ki Kim, Min Cheol Park
IgE-mediated mast cell degranulation and excessive Th2 cells activation are major features of various allergic diseases. Sohamhyoong-tang has been reported to have anti-inflammatory and antibacterial effects. In this study, we investigated the inhibitory effect of Sohamhyoong-tang extract (SHHTE) on allergic symptoms and inflammatory responses in ovalbumin- (OVA-) sensitized BALB/c mice. The mice were sensitized with OVA and alum at 2-week intervals and then orally given SHHTE for 13 days followed by intradermal OVA injection...
2016: Evidence-based Complementary and Alternative Medicine: ECAM
https://www.readbyqxmd.com/read/27350570/dedicator-of-cytokinesis-8-regulates-signal-transducer-and-activator-of-transcription-3-activation-and-promotes-th17%C3%A2-cell-differentiation
#19
Sevgi Keles, Louis Marie Charbonnier, Venkataraman Kabaleeswaran, Ismail Reisli, Ferah Genel, Nesrin Gulez, Waleed Al-Herz, Narayanaswamy Ramesh, Antonio Perez-Atayde, Neslihan E Karaca, Necil Kutukculer, Hao Wu, Raif S Geha, Talal A Chatila
BACKGROUND: The autosomal recessive hyper-IgE syndrome (HIES) caused by dedicator of cytokinesis 8 (DOCK8) deficiency shares clinical features with autosomal dominant HIES because of signal transducer and activator of transcription 3 (STAT3) mutations, including recurrent infections and mucocutaneous candidiasis, which are suggestive of TH17 cell dysfunction. The mechanisms underlying this phenotypic overlap are unclear. OBJECTIVE: We sought to elucidate common mechanisms operating in the different forms of HIES...
November 2016: Journal of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/27315768/staphylococcal-serine-protease-like-proteins-are-pacemakers-of-allergic-airway-reactions-to-staphylococcus-aureus
#20
Sebastian Stentzel, Andrea Teufelberger, Maria Nordengrün, Julia Kolata, Frank Schmidt, Koen van Crombruggen, Stephan Michalik, Jana Kumpfmüller, Sebastian Tischer, Thomas Schweder, Michael Hecker, Susanne Engelmann, Uwe Völker, Olga Krysko, Claus Bachert, Barbara M Bröker
BACKGROUND: A substantial subgroup of asthmatic patients have "nonallergic" or idiopathic asthma, which often takes a severe course and is difficult to treat. The cause might be allergic reactions to the gram-positive pathogen Staphylococcus aureus, a frequent colonizer of the upper airways. However, the driving allergens of S aureus have remained elusive. OBJECTIVE: We sought to search for potentially allergenic S aureus proteins and characterize the immune response directed against them...
May 10, 2016: Journal of Allergy and Clinical Immunology
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