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https://www.readbyqxmd.com/read/28917991/enhanced-expression-of-pd-l1-and-ifn-%C3%AE-on-dendritic-cells-is-associated-with-bcg-induced-th2-inhibition
#1
A C C Gouveia, F G Braga, M Mota, F M C Silva, A S S Brugiolo, E E Oliveira, M C Ayupe, H C Teixeira, A P Ferreira
Accumulating evidence indicates that the exposure to Mycobacterium bovis bacillus Calmette-Guérin (BCG) prevents the development of allergy and the airway dendritic cells (DCs) may be involved in this protective effect. However, studies to better characterize the specific interactions between BCG and DCs and their role in this mycobacteria-mediated Th2 cell suppression are still ongoing. This study aimed to evaluate the effect of the neonatal BCG vaccination in the innate immune response in a mouse model of ovalbumin (OVA)-induced airway inflammation...
September 14, 2017: Cytokine
https://www.readbyqxmd.com/read/28910970/antibody-therapy-for-the-management-of-severe-asthma-with-eosinophilic-inflammation
#2
Ken Ohta, Hiroyuki Nagase, Maho Suzukawa, Shin Ohta
One of the characteristic features of asthma is chronic airway inflammation typically with eosinophil infiltration. Most asthmatics can be treated successfully with conventional treatment appropriate for their severity, but in some severe cases, asthma cannot be well controlled even with thorough treatment and this condition is known as 'refractory asthma'. To overcome severe refractory asthma, a new therapeutic strategy with biologics has been developed based on the knowledge of molecular mechanisms of airway inflammation in asthma, induced by the condition of high Th2-type responses and activation of eosinophils as well as allergic reactions...
July 1, 2017: International Immunology
https://www.readbyqxmd.com/read/28877024/moving-upstream-anti-tslp-in-persistent-uncontrolled-asthma
#3
EDITORIAL
Elisabeth H Bel
New England Journal of Medicine, Volume 377, Issue 10, Page 989-991, September 2017.
September 7, 2017: New England Journal of Medicine
https://www.readbyqxmd.com/read/28877011/tezepelumab-in-adults-with-uncontrolled-asthma
#4
Jonathan Corren, Jane R Parnes, Liangwei Wang, May Mo, Stephanie L Roseti, Janet M Griffiths, René van der Merwe
BACKGROUND: In some patients with moderate-to-severe asthma, particularly those with noneosinophilic inflammation, the disease remains uncontrolled. This trial evaluated the efficacy and safety of tezepelumab (AMG 157/MEDI9929), a human monoclonal antibody specific for the epithelial-cell-derived cytokine thymic stromal lymphopoietin (TSLP), in patients whose asthma remained uncontrolled despite treatment with long-acting beta-agonists and medium-to-high doses of inhaled glucocorticoids...
September 7, 2017: New England Journal of Medicine
https://www.readbyqxmd.com/read/28867182/deficiency-of-klf4-compromises-the-lung-function-in-an-acute-mouse-model-of-allergic-asthma
#5
Jeanette A Nimpong, Wintana Gebregziabher, Udai P Singh, Prakash Nagarkatti, Mitzi Nagarkatti, Johnie Hodge, Chunming Liu, Daping Fan, Walden Ai
Asthma is a chronic inflammatory disease of the airways and the mechanisms are not fully understood. Myeloid-derived suppressor cells (MDSCs) are a heterogeneous group of monocytes, granulocyte and myeloid cells at early stage of differentiation. They possess phenotypic plasticity and regulate airway inflammation. We recently reported that Kruppel-like factor 4 (KLF4) regulates MDSC differentiation into fibrocytes, emerging effectors in chronic inflammation. However, the role of KLF4 in asthma is not known...
August 31, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28861617/novel-therapeutic-approaches-to-atopic-dermatitis
#6
REVIEW
Katarzyna Osinka, Karolina Dumycz, Bartłomiej Kwiek, Wojciech Feleszko
Atopic dermatitis (AD) is one of the most common inflammatory skin diseases. The number of people affected by AD is relatively high and seems to be rising. Although mild and moderate forms of the disease can be well controlled by the use of emollients, topical corticosteroids, and topical calcineurin inhibitors, treatment of severe is still a huge challenge. The new hope is biologic drugs, magic bullets in allergy, targeted at different points of the complex pathomechanism of inflammation in AD. In this review, novel biologic therapies are discussed, including recombinant monoclonal antibodies directed against various interleukin pathways (such as IL-4, IL-13, TSLP, IL-31, and IL-12/23), on immunoglobulin E, molecules acting as T cells, B cells, etc...
August 31, 2017: Archivum Immunologiae et Therapiae Experimentalis
https://www.readbyqxmd.com/read/28853956/new-and-emerging-targeted-systemic-therapies-a-new-era-for-atopic-dermatitis
#7
Dylan E Lee, Ashley K Clark, Khiem A Tran, Vivian Y Shi
PURPOSE: This is a review of emerging targeted, systemic therapies for atopic dermatitis (AD). The information presented aims to provide dermatologists with updated therapeutic options, stimulate academic interest, and spark future research. MATERIALS AND METHODS: Extensive search of ClinicalTrials.gov, the National Eczema Association, and PubMed was performed for clinical trials examining the effect of emerging targeted, systemic therapies in patients with AD. Results were included if they demonstrated efficacy in reversing AD symptoms...
August 30, 2017: Journal of Dermatological Treatment
https://www.readbyqxmd.com/read/28853918/human-bronchial-epithelial-cell-derived-factors-from-severe-asthmatic-subjects-stimulate-eosinophil-differentiation
#8
Brittany M A Salter, Steven G Smith, Manali Mukherjee, Sophie Plante, Sakktee Krisna, Graeme Nusca, John Paul Oliveria, Anam Irshad, Gail M Gauvreau, Jamila Chakir, Parameswaran Nair, Roma Sehmi
RATIONALE: Activated bronchial epithelial cells release alarmins, including thymic stromal lymphopoietin (TSLP) that drive type 2 inflammatory responses. We hypothesize that bronchial epithelial-derived factors enhance in situ eosinophil differentiation and maturation from myeloid precursors, a process that is driven by an IL-5 rich micro-environment within asthma airways. METHODS: To assess the eosinophilopoietic potential of epithelial-derived factors, eosinophil/basophil colony forming units (Eo/B-CFU) were enumerated in 14-day methylcellulose cultures of blood-derived mononuclear cells (NAMNCs) incubated with bronchial epithelial cell supernatants (BECSN) from healthy non-atopic controls (NC; n = 8), mild atopic asthmatics (MA; n = 9) and severe asthmatics (SA; n = 5)...
August 30, 2017: American Journal of Respiratory Cell and Molecular Biology
https://www.readbyqxmd.com/read/28833576/towards-the-development-of-a-rnai-based-topical-treatment-for-psoriasis-proof-of-concept-in-a-3d-psoriasis-skin-model
#9
Desmet Eline, Mireille Van Gele, Lynda Grine, Katrien Remaut, Jo Lambert
RNA interference has emerged as a powerful tool for therapeutic gene silencing, as it offers the possibility to silence virtually any known pathology-causing gene. However, in vivo delivery of RNAi molecules is hampered by their unfavorable physicochemical characteristics and susceptibility to degradation by endogenous enzymes. To overcome these limitations, we recently developed an elastic liposomal formulation, called DDC642, as topical delivery system of therapeutic RNAi molecules for skin disorders. In this study, we validated the therapeutic efficacy of DDC642-encapsulated RNAi molecules in the treatment of psoriasis using three different in vitro models: a standardized keratinocyte monolayer culture, psoriasis-induced keratinocytes and a psoriasis reconstructed skin model...
August 20, 2017: Experimental Dermatology
https://www.readbyqxmd.com/read/28833499/manifestation-of-atopic-dermatitis-like-skin-in-tncb-induced-nc-nga-mice-is-ameliorated-by-topical-treatment-of-substance-p-possibly-through-blockade-of-allergic-inflammation
#10
Hyeongwon Choi, Dong-Jin Kim, Seungwoo Nam, Sunki Lim, Jae-Sung Hwang, Ki Sook Park, Hyun Sook Hong, Min Kyung Shin, Eunkyung Chung, Youngsook Son
Atopic dermatitis (AD) is a chronic inflammatory skin disorder characterized by intense pruritus and eczematous lesion. In this study, topically applied substance P (SP) significantly alleviated AD-like clinical symptoms in 2, 4, 6-trinitrochlorobenzene (TNCB)-induced dermatitis in NC/Nga mice. This effect was nullified by pre-treatment of the neurokinin-1 receptor (NK-1R) antagonist CP99994. SP treatment significantly reduced the infiltration of mast cells and CD3-positive T cells as well as inflammatory cytokines, such as tumor necrosis factor-α (TNF-α) and thymic stromal lymphopoietin (TSLP), in AD-like skin lesions and decreased the levels of IgE and thymus and activation-regulated chemokine in serum...
August 20, 2017: Experimental Dermatology
https://www.readbyqxmd.com/read/28819104/der-f-31-a-novel-allergen-from-dermatophagoides-farinae-activates-epithelial-cells-and-enhances-lung-resident-group-2-innate-lymphoid-cells
#11
Hui Wang, Jianli Lin, Lu Zeng, Chunyan Ouyang, Pixin Ran, Pingchang Yang, Zhigang Liu
Airway epithelial cell-derived thymic stromal lymphopoietin (TSLP) and IL-33 can enhance lung-resident group 2 innate lymphoid cells (ILC2s), and they play an important role in the development of allergic diseases. This study tests the hypothesis that Der f 31 (Dermatophagoides farinae-31), an allergen, modulates airway epithelial cell functions and increases the frequency of lung ILC2s. Our previous research identified cofilin (Der f 31) as a novel allergen. In this study, we found that recombinant Der f 31 (r-Der f 31) upregulated the expression of co-stimulatory molecules in DCs and promoted Th2-skewed polarization...
August 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28815692/amelioration-of-atopic-like-skin-conditions-in-nc-tnd-mice-by-topical-application-with-distilled-alpinia-intermedia-gagnep-extracts
#12
Yosuke Amagai, Chihiro Katsuta, Yoshihiro Nomura, Kumiko Oida, Kenshiro Matsuda, Hyosun Jang, Ginnae Ahn, Tetsuyoshi Hamasaki, Hiroshi Matsuda, Akane Tanaka
Alpinia intermedia, a perennial plant that belongs to the Zingiberaceae family, has been used in folk medicine for a long time in the southern region of Japan. Because skin care is an effective approach that enables patients to manage their atopic dermatitis (AD), various herbal ingredients with few adverse effects have been evaluated for use in AD patients in recent years. In this study, we examined whether distilled extracts obtained from A. intermedia were beneficial for AD-like skin conditions in NC/Tnd mice...
August 16, 2017: Journal of Dermatology
https://www.readbyqxmd.com/read/28792717/the-relationship-between-serum-tarc-tslp-and-postn-levels-and-childhood-atopic-dermatitis
#13
Pinar Uysal, Fatih Birtekocak, Aslihan Buyukozturk Karul
BACKGROUND: The aim of the study is to evaluate the relationship between serum periostin (POSTN), thymus and activation-regulated chemokine (TARC), and thymic stromal lymphopoietin (TSLP) levels and disease severity and atopy in children with atopic dermatitis. METHODS: Sixty children with atopic dermatitis and 31 healthy controls were included in the study. The disease severity was measured by SCORAD scores. Serum POSTN, TARC, and TSLP levels were measured in all participants...
July 1, 2017: Clinical Laboratory
https://www.readbyqxmd.com/read/28783679/a-tslp-complement-axis-mediates-neutrophil-killing-of-methicillin-resistant-staphylococcus-aureus
#14
Erin E West, Rosanne Spolski, Majid Kazemian, Zu Xi Yu, Claudia Kemper, Warren J Leonard
Community-acquired Staphylococcus aureus infections often present as serious skin infections in otherwise healthy individuals and have become a worldwide epidemic problem fueled by the emergence of strains with antibiotic resistance, such as methicillin-resistant S. aureus (MRSA). The cytokine thymic stromal lymphopoietin (TSLP) is highly expressed in the skin and in other barrier surfaces and plays a deleterious role by promoting T helper cell type 2 (TH2) responses during allergic diseases; however, its role in host defense against bacterial infections has not been well elucidated...
November 18, 2016: Science Immunology
https://www.readbyqxmd.com/read/28774591/topical-ror-inverse-agonists-suppress-inflammation-in-mouse-models-of-atopic-dermatitis-and-acute-irritant-dermatitis
#15
Jun Dai, Min-Kyung Choo, Jin Mo Park, David E Fisher
The retinoic acid receptor-related orphan receptors RORα and RORγ are critical for the functions of specific subsets of T cells and innate lymphoid cells, which are key drivers of inflammatory disease in barrier tissues. Here, we investigate the anti-inflammatory potential of SR1001, a synthetic RORα/γ inverse agonist, in mouse models of atopic dermatitis and acute irritant dermatitis. Topical treatment with SR1001 reduces epidermal and dermal features of MC903-induced atopic dermatitis-like disease, and suppresses the production of type 2 cytokines and other inflammatory mediators in lesional skin...
July 31, 2017: Journal of Investigative Dermatology
https://www.readbyqxmd.com/read/28769924/thymic-stromal-lymphopoietin-is-critical-for-regulation-of-proinflammatory-cytokine-response-and-resistance-to-experimental-trypanosoma-congolense-infection
#16
Chukwunonso Onyilagha, Rani Singh, Abdelilah Soussi Gounni, Jude Ezeh Uzonna
African trypanosomiasis (sleeping sickness) poses serious threat to human and animal health in sub-Saharan Africa. Because there is currently no vaccine for preventing this disease and available drugs are not safe, understanding the mechanisms that regulate resistance and/or susceptibility to the disease could reveal novel targets for effective disease therapy and prevention. Thymic stromal lymphopoietin (TSLP) plays a critical role in driving Th2 immune response. Although susceptibility to experimental Trypanosoma congolense infection in mice is associated with excessive proinflammatory responses due in part to impaired Th2 response, the role of TSLP in resistance to African trypanosomiasis has not been well studied...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28765890/fine-particulate-matter-aggravates-allergic-airway-inflammation-through-thymic-stromal-lymphopoietin-activation-in-mice
#17
Yan Liu, Gan-Zhu Feng, Qiang Du, Xiao-Xiang Jin, Xing-Ran Du
Fine particulate matter (PM2.5) has been linked to exacerbation of allergic airway inflammation in mice. However, the mechanism underlying exposure to PM2.5 and subsequent and adverse effects remains to be fully elucidated. Therefore, the present study aimed to investigate the effects of PM2.5 by different levels on airway inflammation in mouse models of in allergic and steroid‑resistant asthma. BALB/c mice were nasally instilled with PBS (control) or 10, 31.6 or 100 µg PM2.5, and randomly assigned into nine groups...
October 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28757265/pathophysiology-of-eosinophilic-esophagitis
#18
Kelly M O'Shea, Seema S Aceves, Evan S Dellon, Sandeep K Gupta, Jonathan M Spergel, Glenn T Furuta, Marc E Rothenberg
Eosinophilic esophagitis (EoE) is an emerging disease that is distinguished from gastroesophageal reflux disease (GERD) by the expression of a unique esophageal transcriptome and the interplay of early life environmental factors with distinct genetic susceptibility elements at 5q22 (TSLP) and 2p23 (CAPN14). Rare genetic syndromes have uncovered the contribution of barrier disruption, mediated in part by defective desmosomes and dysregulated transforming factor beta (TGF-β) production and signaling, to EoE pathophysiology...
July 27, 2017: Gastroenterology
https://www.readbyqxmd.com/read/28746197/role-of-thymic-stromal-lymphopoietin-in-the-pathogenesis-of-lumbar-disc-degeneration
#19
Yu Wang, Xiao-Dong Yi, Chun-De Li
BACKGROUND: This study aims to investigate the role of thymic stromal lymphopoietin (TSLP) in the pathogenesis of lumbar disc degeneration (LDD). METHODS: Nucleus pulposus tissues were collected from 77 LDD patients (the case group), in addition, normal tissues were extracted from 21 patients suffering from lumbar fractures (the control group). Immunohistochemistry was applied in order to detect TSLP positive expression. In accordance with varying transfection, the cells were divided into TSLP-siRNA, TSLP-siRNA + TSLPR-siRNA, control, blank, anti-TSLPR, and IgG groups...
July 2017: Medicine (Baltimore)
https://www.readbyqxmd.com/read/28736555/%C3%AE-glucan-size-controls-dectin-1-mediated-immune-responses-in-human-dendritic-cells-by-regulating-il-1%C3%AE-production
#20
Matthew J Elder, Steve J Webster, Ronnie Chee, David L Williams, J S Hill Gaston, Jane C Goodall
Dectin-1/CLEC7A is a pattern recognition receptor that recognizes β-1,3 glucans, and its stimulation initiates signaling events characterized by the production of inflammatory cytokines from human dendritic cells (DCs) required for antifungal immunity. β-glucans differ greatly in size, structure, and ability to activate effector immune responses from DC; as such, small particulate β-glucans are thought to be poor activators of innate immunity. We show that β-glucan particle size is a critical factor contributing to the secretion of cytokines from human DC; large β-glucan-stimulated DC generate significantly more IL-1β, IL-6, and IL-23 compared to those stimulated with the smaller β-glucans...
2017: Frontiers in Immunology
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