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https://www.readbyqxmd.com/read/29333270/lessons-from-ten-years-of-genome-wide-association-studies-of-asthma
#1
REVIEW
Cristina T Vicente, Joana A Revez, Manuel A R Ferreira
Twenty-five genome-wide association studies (GWAS) of asthma were published between 2007 and 2016, the largest with a sample size of 157242 individuals. Across these studies, 39 genetic variants in low linkage disequilibrium (LD) with each other were reported to associate with disease risk at a significance threshold of P<5 × 10-8, including 31 in populations of European ancestry. Results from analyses of the UK Biobank data (n=380 503) indicate that at least 28 of the 31 associations reported in Europeans represent true-positive findings, collectively explaining 2...
December 2017: Clinical & Translational Immunology
https://www.readbyqxmd.com/read/29320511/application-of-a-phenotypic-drug-discovery-strategy-to-identify-biological-and-chemical-starting-points-for-inhibition-of-tslp-production-in-lung-epithelial-cells
#2
Adelina Orellana, Vicente García-González, Rosa López, Sonia Pascual-Guiral, Estrella Lozoya, Julia Díaz, Daniel Casals, Antolín Barrena, Stephane Paris, Miriam Andrés, Victor Segarra, Dolors Vilella, Rajneesh Malhotra, Paul Eastwood, Anna Planagumà, Montserrat Miralpeix, Arsenio Nueda
Thymic stromal lymphopoietin (TSLP) is a cytokine released by human lung epithelium in response to external insult. Considered as a master switch in T helper 2 lymphocyte (Th2) mediated responses, TSLP is believed to play a key role in allergic diseases including asthma. The aim of this study was to use a phenotypic approach to identify new biological and chemical starting points for inhibition of TSLP production in human bronchial epithelial cells (NHBE), with the objective of reducing Th2-mediated airway inflammation...
2018: PloS One
https://www.readbyqxmd.com/read/29318959/novel-biological-therapies-in-severe-asthma-targeting-the-right-trait
#3
Gilda Varricchi, Giancarlo Marone, Giuseppe Spadaro, Michele Russo, Francescopaolo Granata, Arturo Genovese, Gianni Marone
Asthma is a heterogeneous disease characterized by chronic airway inflammation that results in a wide spectrum of clinical manifestations. Patients with severe asthma represent a substantial share of consumption of healthcare resources and hospitalization. Moreover, these patients are at risk of increased morbidity and mortality. Recently, several phenotypes and endotypes of asthma have been identified. The identification of specific subtypes of asthma is fundamental for optimizing the clinical benefit of novel treatments...
January 9, 2018: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/29312588/tripterygium-wilfordii-inhibits-tonsillar-iga-production-by-downregulating-iga-class-switching-in-iga-nephropathy
#4
Huining Li, Dan Kong, Yangyang Xu, Xiaomei Li, Guodong Yao, Kexin Chen, Qi You, Qingtao Shi, Lei Zhang, Xin Wang, Dawei Yuan, Shusheng Miao, Jingshu Geng, Xiaoming Jin, Hongxue Meng
IgA nephropathy (IgAN) is characterized by high serum IgA levels and IgA deposition in the renal mesangium. Recent research has indicated that pathogenic IgA may originate from affected tonsils, where present enhancement of IgA production by IgA class switching and immuno-activation. Tripterygium Wilfordii (TW) was found to be especially effective in IgAN by its' immunosuppression effect. Given this background, we investigated the mechanisms underlying the role of TW in the generation of IgA and IgA class switching in tonsillar GCs of IgAN patients...
December 12, 2017: Oncotarget
https://www.readbyqxmd.com/read/29310423/phloxine-o-a-cosmetic-colorant-suppresses-the-expression-of-thymic-stromal-lymphopoietin-and-acute-dermatitis-symptoms-in-mice
#5
Hye Eun Lee, Gabsik Yang, Kyu-Bong Kim, Byung-Mu Lee, Joo Young Lee
Cosmetics are primarily applied to the skin; therefore, the association of cosmetic dyes with skin diseases or inflammation is a topic of great interest. Thymic stromal lymphopoietin (TSLP) is an interleukin 7-like cytokine that activates dendritic cells to promote Th2 inflammatory immune responses. TSLP is highly expressed in keratinocytes under inflammatory conditions, which suggests that it may play a critical role in the development of skin diseases, such as atopic dermatitis. Therefore, we investigated whether cosmetic dyes influenced the production of TSLP by keratinocytes...
January 9, 2018: Biomolecules & Therapeutics
https://www.readbyqxmd.com/read/29296821/progenitor-b-1-b-cell-acute-lymphoblastic-leukemia-is-associated-with-collaborative-mutations-in-3-critical-pathways
#6
Sheryl M Gough, Liat Goldberg, Marbin Pineda, Robert L Walker, Yuelin J Zhu, Sven Bilke, Yang Jo Chung, Joseph Dufraine, Subhadip Kundu, Elad Jacoby, Terry J Fry, Susanna Fischer, Renate Panzer-Grümayer, Paul S Meltzer, Peter D Aplan
B-1 and B-2 lymphocytes are derived from distinct developmental pathways and represent layered arms of the innate and adaptive immune systems, respectively. In contrast to a majority of murine B-cell malignancies, which stain positive with the B220 antibody, we discovered a novel form of B-cell leukemia in NUP98-PHF23 (NP23) transgenic mice. The immunophenotype (Lin- B220- CD19+ AA4.1+) was identical to that of progenitor (pro) B-1 cells, and VH gene usage was skewed toward 3' V regions, similar to murine fetal liver B cells...
September 12, 2017: Blood Advances
https://www.readbyqxmd.com/read/29296700/il-33-il-25-and-tslp-induce-a-distinct-phenotypic-and-activation-profile-in-human-type-2-innate-lymphoid-cells
#7
Ana Camelo, Guglielmo Rosignoli, Yoichiro Ohne, Ross A Stewart, Catherine Overed-Sayer, Matthew A Sleeman, Richard D May
Innate lymphoid cells (ILCs) represent a distinct branch of the lymphoid lineage composed of 3 major subpopulations: ILC1, ILC2, and ILC3. ILCs are mainly described as tissue-resident cells but can be detected at low levels in human blood. However, unlike mouse ILCs, there is still no consistent methodology to purify and culture these cells that enables in-depth analysis of their intrinsic biology. Here, we describe defined culture conditions for ILC2s, which allowed us to dissect the roles of interleukin 2 (IL-2), IL-25, IL-33, and thymic stromal lymphopoietin (TSLP) individually, or in combination, in modulating ILC2 phenotype and function...
April 11, 2017: Blood Advances
https://www.readbyqxmd.com/read/29279286/egfr-transactivation-is-involved-in-tnf-%C3%AE-induced-expression-of-thymic-stromal-lymphopoietin-in-human-keratinocyte-cell-line
#8
Ryosuke Segawa, Kenichi Shigeeda, Takahiro Hatayama, Jiangxu Dong, Natsumi Mizuno, Takahiro Moriya, Masahiro Hiratsuka, Noriyasu Hirasawa
BACKGROUND: Thymic stromal lymphopoietin (TSLP) is an epithelial cell-derived cytokine involved in the pathology of inflammatory skin diseases, such as atopic dermatitis and psoriasis. Tumor necrosis factor (TNF)-α, a key cytokine in inflammatory skin diseases, is a known TSLP inducer. TNF-α activates NF-κB and induces transactivation of epidermal growth factor receptor (EGFR) in epithelial cells. However, the detailed mechanism of TSLP induction by TNF-α has remained unclear. OBJECTIVE: We investigated the involvement of TNF-α-induced EGFR transactivation in TSLP expression...
December 18, 2017: Journal of Dermatological Science
https://www.readbyqxmd.com/read/29273672/cd1a-presentation-of-endogenous-antigens-by-group-2-innate-lymphoid-cells
#9
Clare S Hardman, Yi-Ling Chen, Maryam Salimi, Rachael Jarrett, David Johnson, Valtteri J Järvinen, Raymond J Owens, Emmanouela Repapi, David J Cousins, Jillian L Barlow, Andrew N J McKenzie, Graham Ogg
Group 2 innate lymphoid cells (ILC2) are effectors of barrier immunity, with roles in infection, wound healing, and allergy. A proportion of ILC2 express MHCII (major histocompatibility complex II) and are capable of presenting peptide antigens to T cells and amplifying the subsequent adaptive immune response. Recent studies have highlighted the importance of CD1a-reactive T cells in allergy and infection, activated by the presentation of endogenous neolipid antigens and bacterial components. Using a human skin challenge model, we unexpectedly show that human skin-derived ILC2 can express CD1a and are capable of presenting endogenous antigens to T cells...
December 22, 2017: Science Immunology
https://www.readbyqxmd.com/read/29272985/the-expression-of-thymic-stromal-lymphopoietin-in-patients-and-animal-models-with-eosinophilic-otitis-media
#10
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
https://www.readbyqxmd.com/read/29259025/noncanonical-nf-%C3%AE%C2%BAb-signaling-and-the-essential-kinase-nik-modulate-crucial-features-associated-with-eosinophilic-esophagitis-pathogenesis
#11
Kristin Eden, Daniel E Rothschild, Dylan K McDaniel, Bettina Heid, Irving C Allen
Eosinophilic esophagitis (EoE) is an allergic disease of the esophagus driven by T cell and eosinophil responses to dietary allergens, resulting in chronic mucosal inflammation. Few spontaneous animal models of esophageal eosinophilia exist, with most studies relying on artificial sensitization procedures. NF-κB-inducing kinase (NIK; MAP3K14) is a key signaling molecule of the noncanonical NF-κB (NFKB1) pathway, an alternative signaling cascade producing chemokines involved in lymphoid stroma development and leukocyte trafficking...
December 19, 2017: Disease Models & Mechanisms
https://www.readbyqxmd.com/read/29250181/human-thymic-stromal-lymphopoietin-promotes-the-proliferation-and-invasion-of-cervical-cancer-cells-by-downregulating-microrna-132-expression
#12
Wen-Jie Zhou, Hui-Li Yang, Kai-Kai Chang, Yi Meng, Ming-Yan Wang, Min-Min Yuan, Ming-Qing Li, Feng Xie
Thymic stromal lymphopoietin (TSLP), produced by cervical cancer (CC) cells, promotes angiogenesis, and the recruitment and functional regulation of eosinophils. It has been reported that microRNA (miR)-132 is aberrantly decreased in CC tissues. However, the function and mechanism of TSLP on the biological behaviors of CC cells is largely unknown. The aim of the present study was to investigate the effect of TSLP on the expression of miR-132 and the proliferation and invasion in vitro of CC cell lines, namely, HeLa and SiHa cells...
December 2017: Oncology Letters
https://www.readbyqxmd.com/read/29250125/yi-qi-ping-chuan-fang-reduces-tslp-elevation-caused-by-lps-poly-i-c-via-inhibiting-tlr4-myd88-nf-%C3%AE%C2%BAb-signaling-pathway
#13
Minye Qu, Xiang Tao, Jian Ma
Objective: To explore the correlation between Thymic Stromal Lymphopoietin (TSLP) and the Nuclear Factor- (NF-) κB signaling pathways in bronchial epithelial cells and to clarify whether the traditional Chinese medicine formula Yi-Qi-Ping-Chuan-Fang (YQPC) reduces inflammation by inhibiting TSLP/NF-κB signaling pathways. Methods: Cells were stimulated with LPS + Poly(I:C) and treated with YQPC. The expressions of TSLP and NF-κB signaling pathways related proteins P65, IκK, IκBa, P-P65, P-IκK, P-IκBa were detected...
2017: Evidence-based Complementary and Alternative Medicine: ECAM
https://www.readbyqxmd.com/read/29248519/t-cell-inhibitors-for-atopic-dermatitis
#14
W James Tidwell, Joseph F Fowler
The management of atopic dermatitis is changing with the development of novel biological agents to target specific molecules in the inflammatory cascade. Dupilumab has proven its ability to act on the IL-4 receptor in treating atopic dermatitis. Thymic stromal lymphopoietin (TSLP) monoclonal antibody (AMG157/ MEDI9929) and OX40 blocking antibody (GBR 830) were developed by target the same pathway as dupilumab. The clinical data on the efficacy for these drugs is not yet known. There is some early evidence that AMG157/ MEDI9929 attenuates most measures of allergen-induced asthmatic responses...
December 14, 2017: Journal of the American Academy of Dermatology
https://www.readbyqxmd.com/read/29235163/ultraviolet-b-eye-irradiation-aggravates-atopic-dermatitis-via-acth-and-nlrp3-inflammasome-in-nc-nga-mice
#15
Keiichi Hiramoto, Yurika Yamate, Satoshi Yokoyama
BACKGROUND: Ultraviolet (UV) B irradiation has been shown to improve atopic dermatitis (AD). However, the relationship between UVB eye irradiation and AD is not known. This issue was addressed using a mouse model of AD. METHODS: The eyes of NC/Nga mice were irradiated with UVB at a dose of 1.0 kJ/m2 using a 20SE sunlamp for the duration of the experimental period. RESULTS: AD symptoms deteriorated upon UVB eye irradiation. The levels of adrenocorticotropic hormone (ACTH) in the plasma and nucleotide-binding domain and leucine-rich-containing family, pyrin domain-containing (NLRP)3 and neutrophil markers in the skin were increased in UVB-irradiated mice...
December 13, 2017: Photodermatology, Photoimmunology & Photomedicine
https://www.readbyqxmd.com/read/29227500/enhanced-topical-delivery-of-dexamethasone-by-%C3%AE-cyclodextrin-decorated-thermoresponsive-nanogels
#16
M Giulbudagian, S Hönzke, J Bergueiro, D Işık, F Schumacher, S Saeidpour, S B Lohan, M C Meinke, C Teutloff, M Schäfer-Korting, G Yealland, B Kleuser, S Hedtrich, M Calderón
Highly hydrophilic, responsive nanogels are attractive as potential systems for the topical delivery of bioactives encapsulated in their three-dimensional polymeric scaffold. Yet, these drug carrier systems suffer from drawbacks for efficient delivery of hydrophobic drugs. Addressing this, β-cyclodextrin (βCD) could be successfully introduced into the drug carrier systems by exploiting its unique affinity toward dexamethasone (DXM) as well as its role as topical penetration enhancer. The properties of βCD could be combined with those of thermoresponsive nanogels (tNGs) based on dendritic polyglycerol (dPG) as a crosslinker and linear thermoresponsive polyglycerol (tPG) inducing responsiveness to temperature changes...
December 11, 2017: Nanoscale
https://www.readbyqxmd.com/read/29222519/virtual-screening-for-inhibitors-of-the-human-tslp-tslpr-interaction
#17
Dries Van Rompaey, Kenneth Verstraete, Frank Peelman, Savvas N Savvides, Koen Augustyns, Pieter Van Der Veken, Hans De Winter
The pro-inflammatory cytokine thymic stromal lymphopoietin (TSLP) plays a pivotal role in the pathophysiology of various allergy disorders that are mediated by type 2 helper T cell (Th2) responses, such as asthma and atopic dermatitis. TSLP forms a ternary complex with the TSLP receptor (TSLPR) and the interleukin-7-receptor subunit alpha (IL-7Rα), thereby activating a signaling cascade that culminates in the release of pro-inflammatory mediators. In this study, we conducted an in silico characterization of the TSLP:TSLPR complex to investigate the drugability of this complex...
December 8, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29221590/activit%C3%A3-s-immunomodulatrice-anti-inflammatoire-antiprurigineuse-et-tol%C3%A3-rog%C3%A3-nique-induites-par-i-modulia%C3%A2-un-extrait-issu-de-culture-d%C3%A2-aquaphilus-dolomiae-dans-les-mod%C3%A3-les-pharmacologiques-de-dermatite-atopique-immunomodulatory-anti-inflammatory-anti-pruritus
#18
T Nguyen, N Castex-Rizzi, D Redoulès
Atopic dermatitis (AD) is an inflammatory and pruritic dermatosis of multifactorial origin. Topical steroids are the first line treatment for severe AD however alternatives treatment are increasingly needed. A biological concentrate was elaborated from culture of an Avène aquatic microflora isolate namely Aquaphilus dolomiae. Numerous extracts were evaluated in relevant AD in vitro models with human keratinocytes. Among these extracts, a particular one I-modulia® was found to be remarkable in terms of pharmacological activities: innate immunity modulating by agonizing Toll like receptor (TLR)2, TLR4 and TLR5, induction of anti-microbial peptides, inhibition of cytokines characteristics of T helper (Th)1, Th2 and Th17 responses, inhibition of Protease-activated-receptor (PAR) 2 and Thymic-stromal-lymphopoeitin (TSLP) both being known to be upregulated in pruritus...
January 2017: Annales de Dermatologie et de Vénéréologie
https://www.readbyqxmd.com/read/29220720/induction-of-thymic-stromal-lymphopoietin-by-a-steroid-alkaloid-derivative-in-mouse-keratinocytes
#19
Yan Weng, Natsumi Mizuno, Jiangxu Dong, Ryosuke Segawa, Takayuki Yonezawa, Byung Yoon Cha, Je-Tae Woo, Takahiro Moriya, Masahiro Hiratsuka, Noriyasu Hirasawa
Thymic stromal lymphopoietin (TSLP) plays critical roles in inducing and exacerbating allergic diseases. Chemical compounds that induce TSLP production can enhance sensitization to antigens and exacerbate allergic inflammation. Hence, identifying such chemicals will be important to prevent an increase in allergic diseases. In the present study, we found, for the first time, that a steroid alkaloid derivative, code no. 02F04, concentration and time dependently induced mRNA expression and production of TSLP in a mouse keratinocyte cell line, PAM212...
December 5, 2017: International Immunopharmacology
https://www.readbyqxmd.com/read/29217133/pge2-suppresses-human-group-2-innate-lymphoid-cell-function
#20
Jovana Maric, Avinash Ravindran, Luca Mazzurana, Åsa K Björklund, Aline Van Acker, Anna Rao, Danielle Friberg, Sven-Erik Dahlén, Akos Heinemann, Viktoria Konya, Jenny Mjösberg
BACKGROUND: Group 2 innate lymphoid cells (ILC2) are involved in the initial phase of type 2 inflammation and can amplify allergic immune responses by orchestrating other type 2 immune cells. PGE2 is a bioactive lipid that plays protective roles in the lung, particularly during allergic inflammation. OBJECTIVE: We set out to investigate how PGE2 regulates human ILC2 function. METHODS: The effects of PGE2 on human ILC2 proliferation, intracellular cytokine and transcription factor expression were assessed by flow cytometry...
December 4, 2017: Journal of Allergy and Clinical Immunology
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