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Type 2 innate lymphoid cells

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https://www.readbyqxmd.com/read/28814067/neuro-immune-interactions-in-allergic-diseases-novel-targets-for-therapeutics
#1
Tiphaine Voisin, Amélie Bouvier, Isaac M Chiu
Recent studies have highlighted an emerging role for neuro-immune interactions in mediating allergic diseases. Allergies are caused by an overactive immune response to a foreign antigen. The peripheral sensory and autonomic nervous system densely innervates mucosal barrier tissues including the skin, respiratory tract and gastrointestinal (GI) tract that are exposed to allergens. It is increasingly clear that neurons actively communicate with and regulate the function of mast cells, dendritic cells, eosinophils, Th2 cells and type 2 innate lymphoid cells in allergic inflammation...
June 1, 2017: International Immunology
https://www.readbyqxmd.com/read/28811323/il-22-induces-reg3%C3%AE-and-inhibits-allergic-inflammation-in-house-dust-mite-induced-asthma-models
#2
Takashi Ito, Koichi Hirose, Aiko Saku, Kenta Kono, Hiroaki Takatori, Tomohiro Tamachi, Yoshiyuki Goto, Jean-Christophe Renauld, Hiroshi Kiyono, Hiroshi Nakajima
Previous studies have shown that IL-22, one of the Th17 cell-related cytokines, plays multiple roles in regulating allergic airway inflammation caused by antigen-specific Th2 cells; however, the underlying mechanism remains unclear. Here, we show that allergic airway inflammation and Th2 and Th17 cytokine production upon intratracheal administration of house dust mite (HDM) extract, a representative allergen, were exacerbated in IL-22-deficient mice. We also found that IL-22 induces Reg3γ production from lung epithelial cells through STAT3 activation and that neutralization of Reg3γ significantly exacerbates HDM-induced eosinophilic airway inflammation and Th2 cytokine induction...
August 15, 2017: Journal of Experimental Medicine
https://www.readbyqxmd.com/read/28808975/isolation-of-group-2-innate-lymphoid-cells-from-mouse-lungs
#3
Claudia U Duerr, Jörg H Fritz
The recently described group 2 innate lymphoid cells (ILC2) exert critical roles in type 2 immune responses, epithelial repair at mucosal tissues and metabolic homeostasis. ILC2 release large amounts of type 2 cytokines such as interleukin 4 (IL-4), IL-5, and IL-13, driving type 2 immunity such as the defense against helminths. However, if not tightly regulated ILC2 can trigger unwanted type 2 immunopathologies including allergic airway inflammation, airway hyper-responsiveness, and atopic dermatitis. Viral respiratory tract infections, archetypal triggers of type 1 immune responses, often give rise to pulmonary type 2 immunopathologies such as asthma and asthma exacerbations...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28804130/innate-lymphoid-cells-major-players-in-inflammatory-diseases
#4
REVIEW
Mikaël Ebbo, Adeline Crinier, Frédéric Vély, Eric Vivier
Recent years have seen a marked increase in our understanding of innate lymphoid cells (ILCs). ILCs can be classified into different groups based on their similarity to T cell subsets in terms of their expression of key transcription factors and cytokine production. Various immunological functions of ILCs have been described, and increasing numbers of studies have implicated these cells in inflammatory disorders. Here, we detail the roles of ILCs in inflammatory diseases; we cover type 2 inflammatory diseases (such as asthma, chronic rhinosinusitis and atopic dermatitis), as well as inflammatory bowel diseases, psoriasis and other systemic or organ-specific inflammatory and autoimmune diseases...
August 14, 2017: Nature Reviews. Immunology
https://www.readbyqxmd.com/read/28791025/the-ido-ahr-axis-controls-th17-treg-immunity-in-a-pulmonary-model-of-fungal-infection
#5
Eliseu Frank de Araújo, Claudia Feriotti, Nayane Alves de Lima Galdino, Nycolas Willian Preite, Vera Lúcia Garcia Calich, Flávio Vieira Loures
In infectious diseases, the enzyme indoleamine 2,3 dioxygenase-1 (IDO1) that catalyzes the tryptophan (Trp) degradation along the kynurenines (Kyn) pathway has two main functions, the control of pathogen growth by reducing available Trp and immune regulation mediated by the Kyn-mediated expansion of regulatory T (Treg) cells via aryl hydrocarbon receptor (AhR). In pulmonary paracoccidioidomycosis (PCM) caused by the dimorphic fungus Paracoccidioides brasiliensis, IDO1 was shown to control the disease severity of both resistant and susceptible mice to the infection; however, only in resistant mice, IDO1 is induced by TGF-β signaling that confers a stable tolerogenic phenotype to dendritic cells (DCs)...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28783701/ppar-%C3%AE-promotes-type-2-immune-responses-in-allergy-and-nematode-infection
#6
Ting Chen, Christopher A Tibbitt, Xiaogang Feng, Julian M Stark, Leona Rohrbeck, Lisa Rausch, Saikiran K Sedimbi, Mikael C I Karlsson, Bart N Lambrecht, Gunilla B Karlsson Hedestam, Rudi W Hendriks, Benedict J Chambers, Susanne Nylén, Jonathan M Coquet
A hallmark of immunity to worm infections and many allergies is a strong type 2 immune response. This is characterized by the production of cytokines interleukin-5 (IL-5) and IL-13 by adaptive T helper 2 (TH2) cells and/or type 2 innate lymphoid cells. Peroxisome proliferator activated receptor-γ (PPAR-γ) is typically regarded as an anti-inflammatory factor. We report that TH2 cells express high levels of PPAR-γ in response to the allergen house dust mite and after infection with the parasite Heligmosomoides polygyrus Mice lacking PPAR-γ in T cells failed to effectively differentiate into IL-5- and IL-13-secreting cells and, hence, did not develop TH2 cell-associated pathologies, including goblet cell metaplasia and eosinophilia, in response to allergen challenge...
March 10, 2017: Science Immunology
https://www.readbyqxmd.com/read/28774591/topical-ror-inverse-agonists-suppress-inflammation-in-mouse-models-of-atopic-dermatitis-and-acute-irritant-dermatitis
#7
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/28771767/local-il-25-contributes-to-th2-biased-inflammatory-profiles-in-nasal-polyps
#8
H-Y Hong, F-H Chen, Y-Q Sun, X-T Hu, Y Wei, Y-P Fan, J Zhang, D-H Wang, R Xu, H-B Li, J-B Shi
BACKGROUND: IL-25 has been proposed to play a key role in the pathogenesis of chronic rhinosinusitis with nasal polyps (CRSwNP). This study aims to evaluate the association of IL-25 with the Th2-biased inflammatory profiles in CRSwNP. METHODS: Nasal polyp (NP) tissues and control uncinate process tissues were collected from 92 patients with CRSwNP, 20 patients with chronic rhinosinusitis without nasal polyps (CRSsNP), and 16 normal control subjects. IL-25 expression was examined using immunohistochemistry and immunofluorescence staining, flow cytometry, RT-qPCR, and ELISA...
August 3, 2017: Allergy
https://www.readbyqxmd.com/read/28758901/stromal-cell-cadherin-11-regulates-adipose-tissue-inflammation-and-diabetes
#9
Sook Kyung Chang, Ayano C Kohlgruber, Fumitaka Mizoguchi, Xavier Michelet, Benjamin J Wolf, Kevin Wei, Pui Y Lee, Lydia Lynch, Danielle Duquette, Victòria Ceperuelo-Mallafré, Alexander S Banks, Michael B Brenner
M2 macrophages, innate lymphoid type 2 cells (ILC2s), eosinophils, Tregs, and invariant NK T cells (iNKT cells) all help to control adipose tissue inflammation, while M1 macrophages, TNF, and other inflammatory cytokines drive inflammation and insulin resistance in obesity. Stromal cells regulate leukocyte responses in lymph nodes, but the role of stromal cells in adipose tissue inflammation is unknown. PDGFRα+ stromal cells are major producers of IL-33 in adipose tissue. Here, we show that mesenchymal cadherin-11 modulates stromal fibroblast function...
July 31, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28747424/ilc2s-regulate-adaptive-th2-cell-functions-via-pd-l1-checkpoint-control
#10
Christian Schwartz, Adnan R Khan, Achilleas Floudas, Sean P Saunders, Emily Hams, Hans-Reimer Rodewald, Andrew N J McKenzie, Padraic G Fallon
Group 2 innate lymphoid cells (ILC2s) are important effector cells driving the initiation of type 2 immune responses leading to adaptive T helper 2 (Th2) immunity. Here we show that ILC2s dynamically express the checkpoint inhibitor molecule PD-L1 during type 2 pulmonary responses. Surprisingly, PD-L1:PD-1 interaction between ILC2s and CD4(+) T cells did not inhibit the T cell response, but PD-L1-expressing ILC2s stimulated increased expression of GATA3 and production of IL-13 by Th2 cells both in vitro and in vivo...
July 26, 2017: Journal of Experimental Medicine
https://www.readbyqxmd.com/read/28743611/increased-frequencies-of-basophils-type-2-innate-lymphoid-cells-and-th2-cells-in-skin-of-patients-with-atopic-dermatitis-but-not-psoriasis
#11
Shunya Mashiko, Heena Mehta, Robert Bissonnette, Marika Sarfati
BACKGROUND: Pathogenesis of atopic dermatitis (AD) involves interaction between type 2 cells that include basophils, mast cells, innate lymphoid type 2 cells (ILC2), and Th2 cells. Levels of IL-4 and IL-13 are elevated in AD patients. OBJECTIVE: Here, we investigated the distribution of type 2 cells and the source of IL-4 and IL-13 in skin and blood of AD relative to psoriasis. METHODS: Lesional skin biopsies and blood were collected from patients...
July 15, 2017: Journal of Dermatological Science
https://www.readbyqxmd.com/read/28742815/il33-mediated-ilc2-activation-and-neutrophil-il5-production-in-the-lung-response-after-severe-trauma-a-reverse-translation-study-from-a-human-cohort-to-a-mouse-trauma-model
#12
Jing Xu, Jesse Guardado, Rosemary Hoffman, Hui Xu, Rami Namas, Yoram Vodovotz, Li Xu, Mostafa Ramadan, Joshua Brown, Heth R Turnquist, Timothy R Billiar
BACKGROUND: The immunosuppression and immune dysregulation that follows severe injury includes type 2 immune responses manifested by elevations in interleukin (IL) 4, IL5, and IL13 early after injury. We hypothesized that IL33, an alarmin released early after tissue injury and a known regulator of type 2 immunity, contributes to the early type 2 immune responses after systemic injury. METHODS AND FINDINGS: Blunt trauma patients admitted to the trauma intensive care unit of a level I trauma center were enrolled in an observational study that included frequent blood sampling...
July 2017: PLoS Medicine
https://www.readbyqxmd.com/read/28714991/resolution-of-inflammation-by-interleukin-9-producing-type-2-innate-lymphoid-cells
#13
Simon Rauber, Markus Luber, Stefanie Weber, Lisa Maul, Alina Soare, Thomas Wohlfahrt, Neng-Yu Lin, Katharina Dietel, Aline Bozec, Martin Herrmann, Mark H Kaplan, Benno Weigmann, Mario M Zaiss, Ursula Fearon, Douglas J Veale, Juan D Cañete, Oliver Distler, Felice Rivellese, Costantino Pitzalis, Markus F Neurath, Andrew N J McKenzie, Stefan Wirtz, Georg Schett, Jörg H W Distler, Andreas Ramming
Inflammatory diseases such as arthritis are chronic conditions that fail to resolve spontaneously. While the cytokine and cellular pathways triggering arthritis are well defined, those responsible for the resolution of inflammation are incompletely characterized. Here we identified interleukin (IL)-9-producing type 2 innate lymphoid cells (ILC2s) as the mediators of a molecular and cellular pathway that orchestrates the resolution of chronic inflammation. In mice, the absence of IL-9 impaired ILC2 proliferation and activation of regulatory T (Treg) cells, and resulted in chronic arthritis with excessive cartilage destruction and bone loss...
August 2017: Nature Medicine
https://www.readbyqxmd.com/read/28701507/the-innate-cytokines-il-25-il-33-and-tslp-cooperate-in-the-induction-of-type-2-innate-lymphoid-cell-expansion-and-mucous-metaplasia-in-rhinovirus-infected-immature-mice
#14
Mingyuan Han, Charu Rajput, Jun Y Hong, Jing Lei, Joanna L Hinde, Qian Wu, J Kelley Bentley, Marc B Hershenson
Early-life respiratory viral infection is a risk factor for asthma development. Rhinovirus (RV) infection of 6-d-old mice, but not mature mice, causes mucous metaplasia and airway hyperresponsiveness that are associated with the expansion of lung type 2 innate lymphoid cells (ILC2s) and are dependent on IL-13 and the innate cytokine IL-25. However, contributions of the other innate cytokines, IL-33 and thymic stromal lymphopoietin (TSLP), to the observed asthma-like phenotype have not been examined. We reasoned that IL-33 and TSLP expression are also induced by RV infection in immature mice and are required for maximum ILC2 expansion and mucous metaplasia...
August 15, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28689841/biologic-therapy-and-novel-molecular-targets-of-severe-asthma
#15
Amber N Pepper, Harald Renz, Thomas B Casale, Holger Garn
Treatment options for severe or uncontrolled asthma are increasing, especially pertaining to novel biologic therapies. The 2 primary asthma endotypes, T2 high and T2 low, are defined by the level of type 2 T helper and innate lymphoid cell activity and mediators. Most therapies for severe asthma target T2 high asthma, including the 3 biologics approved for use in the United States and Europe: omalizumb, mepolizumb, and reslizumab. Other biologics, with various molecular targets, are under investigation. Unfortunately, treatment options for T2 low asthma are limited...
July 2017: Journal of Allergy and Clinical Immunology in Practice
https://www.readbyqxmd.com/read/28689218/allergic-inflammation-is-exacerbated-by-allergen-induced-type-2-innate-lymphoid-cells-in-a-murine-model-of-allergic-rhinitis
#16
L Lin, F Dai, J J Wei, X Y Tang, Z Chen, G B Sun
BACKGROUND: Group 2 innate lymphoid cells (ILC2s) represent a new innate effector leukocyte population that mediates type-2 immune response. However, the contribution of ILC2s to allergic rhinitis (AR) is currently not well defined. OBJECTIVE: To evaluate the potential existence and function of allergen-induced ILC2s in the experimental AR. METHODS: We established a murine model of AR using ovalbumin (OVA) and aluminium hydroxide. The OVA-induced ILC2s were sorted and purified from the mouse nasal-associated lymphoid tissue (NALT)...
July 9, 2017: Rhinology
https://www.readbyqxmd.com/read/28687373/il-33-and-the-intestine-the-good-the-bad-and-the-inflammatory
#17
REVIEW
Zerina Hodzic, Ellen Merrick Schill, Alexa M Bolock, Misty Good
Interleukin-33 (IL-33) is a member of the IL-1 cytokine family that has been widely studied since its discovery in 2005 for its dichotomous functions in homeostasis and inflammation. IL-33, along with its receptor suppression of tumorigenicity 2 (ST2), has been shown to modulate both the innate and adaptive immune system. Originally, the IL-33/ST2 signaling axis was studied in the context of inducing type 2 immune responses with the expression of ST2 by T helper 2 (TH2) cells. However, the role of IL-33 is not limited to TH2 responses...
July 4, 2017: Cytokine
https://www.readbyqxmd.com/read/28667163/leukotriene-c4-potentiates-il-33-induced-group-2-innate-lymphoid-cell-activation-and-lung-inflammation
#18
Sean J Lund, Alex Portillo, Kellen Cavagnero, Rachel E Baum, Luay H Naji, Jana H Badrani, Amit Mehta, Michael Croft, David H Broide, Taylor A Doherty
Asthma is a complex disease that is promoted by dysregulated immunity and the presence of many cytokine and lipid mediators. Despite this, there is a paucity of data demonstrating the combined effects of multiple mediators in asthma pathogenesis. Group 2 innate lymphoid cells (ILC2s) have recently been shown to play important roles in the initiation of allergic inflammation; however, it is unclear whether lipid mediators, such as cysteinyl leukotrienes (CysLTs), which are present in asthma, could further amplify the effects of IL-33 on ILC2 activation and lung inflammation...
August 1, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28661041/metabolic-control-of-type-2-immunity
#19
REVIEW
Leonard R Pelgrom, Bart Everts
Type 2 immune responses play key roles in protection against parasitic worm infections, whole-body metabolic homeostasis, wound healing, and the development of allergies. As a result, there is considerable interest in understanding the pathways that regulate type 2 immunity in order to identify strategies of targeting and controlling these responses. In recent years, it has become increasingly clear that the functional properties of immune cells, including those involved in type 2 immune responses, are dependent on the engagement of specific metabolic pathways such as aerobic glycolysis and fatty acid oxidation (FAO)...
June 29, 2017: European Journal of Immunology
https://www.readbyqxmd.com/read/28658560/il-33-biological-properties-functions-and-roles-in-airway-disease
#20
REVIEW
Li Yin Drake, Hirohito Kita
Interleukin (IL)-33 is a key cytokine involved in type 2 immunity and allergic airway diseases. Abundantly expressed in lung epithelial cells, IL-33 plays critical roles in both innate and adaptive immune responses in mucosal organs. In innate immunity, IL-33 and group 2 innate lymphoid cells (ILC2s) provide an essential axis for rapid immune responses and tissue homeostasis. In adaptive immunity, IL-33 interacts with dendritic cells, Th2 cells, follicular T cells, and regulatory T cells, where IL-33 influences the development of chronic airway inflammation and tissue remodeling...
July 2017: Immunological Reviews
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