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https://www.readbyqxmd.com/read/28936778/preferential-reduction-of-circulating-innate-lymphoid-cells-type-2-in-patients-with-common-variable-immunodeficiency-with-secondary-complications-is-part-of-a-broader-immune-dysregulation
#1
David Friedmann, Baerbel Keller, Ina Harder, Jonas Schupp, Yakup Tanriver, Susanne Unger, Klaus Warnatz
PURPOSE: Over a third of patients with common variable immunodeficiency (CVID) suffer from secondary complications like inflammatory organ disease, autoimmune manifestations, or lymphoproliferation contributing to increased morbidity and mortality in affected patients. Innate lymphoid cells (ILCs) have emerging roles in setting the milieu for physiological, but also pathological, immune responses and inflammation. We therefore sought to correlate the recently identified disturbed homeostasis of ILCs with alterations of the adaptive immune system in complex CVID patients (CVIDc)...
September 21, 2017: Journal of Clinical Immunology
https://www.readbyqxmd.com/read/28930659/group-1-innate-lymphoid-cell-lineage-identity-is-determined-by-a-cis-regulatory-element-marked-by-a-long-non-coding-rna
#2
Walter K Mowel, Sam J McCright, Jonathan J Kotzin, Magalie A Collet, Asli Uyar, Xin Chen, Alexandra DeLaney, Sean P Spencer, Anthony T Virtue, EnJun Yang, Alejandro Villarino, Makoto Kurachi, Margaret C Dunagin, Gretchen Harms Pritchard, Judith Stein, Cynthia Hughes, Diogo Fonseca-Pereira, Henrique Veiga-Fernandes, Arjun Raj, Taku Kambayashi, Igor E Brodsky, John J O'Shea, E John Wherry, Loyal A Goff, John L Rinn, Adam Williams, Richard A Flavell, Jorge Henao-Mejia
Commitment to the innate lymphoid cell (ILC) lineage is determined by Id2, a transcriptional regulator that antagonizes T and B cell-specific gene expression programs. Yet how Id2 expression is regulated in each ILC subset remains poorly understood. We identified a cis-regulatory element demarcated by a long non-coding RNA (lncRNA) that controls the function and lineage identity of group 1 ILCs, while being dispensable for early ILC development and homeostasis of ILC2s and ILC3s. The locus encoding this lncRNA, which we termed Rroid, directly interacted with the promoter of its neighboring gene, Id2, in group 1 ILCs...
September 19, 2017: Immunity
https://www.readbyqxmd.com/read/28928446/tumour-derived-pgd2-and-nkp30-b7h6-engagement-drives-an-immunosuppressive-ilc2-mdsc-axis
#3
Sara Trabanelli, Mathieu F Chevalier, Amaia Martinez-Usatorre, Alejandra Gomez-Cadena, Bérengère Salomé, Mariangela Lecciso, Valentina Salvestrini, Grégory Verdeil, Julien Racle, Cristina Papayannidis, Hideaki Morita, Irene Pizzitola, Camille Grandclément, Perrine Bohner, Elena Bruni, Mukul Girotra, Rani Pallavi, Paolo Falvo, Elisabeth Oppliger Leibundgut, Gabriela M Baerlocher, Carmelo Carlo-Stella, Daniela Taurino, Armando Santoro, Orietta Spinelli, Alessandro Rambaldi, Emanuela Giarin, Giuseppe Basso, Cristina Tresoldi, Fabio Ciceri, David Gfeller, Cezmi A Akdis, Luca Mazzarella, Saverio Minucci, Pier Giuseppe Pelicci, Emanuela Marcenaro, Andrew N J McKenzie, Dominique Vanhecke, George Coukos, Domenico Mavilio, Antonio Curti, Laurent Derré, Camilla Jandus
Group 2 innate lymphoid cells (ILC2s) are involved in human diseases, such as allergy, atopic dermatitis and nasal polyposis, but their function in human cancer remains unclear. Here we show that, in acute promyelocytic leukaemia (APL), ILC2s are increased and hyper-activated through the interaction of CRTH2 and NKp30 with elevated tumour-derived PGD2 and B7H6, respectively. ILC2s, in turn, activate monocytic myeloid-derived suppressor cells (M-MDSCs) via IL-13 secretion. Upon treating APL with all-trans retinoic acid and achieving complete remission, the levels of PGD2, NKp30, ILC2s, IL-13 and M-MDSCs are restored...
September 19, 2017: Nature Communications
https://www.readbyqxmd.com/read/28921511/bone-marrow-ilc2s-a-local-source-of-il-5-in-il-33-driven-eosinophilia
#4
Kristina Johansson, Carina Malmhäll, Patricia Ramos-Ramírez, Madeleine Rådinger
T helper type 2 (TH 2) cells, type 2 innate lymphoid cells (ILC2s) and eosinophil progenitors have previously been described to produce IL-5 in the airways upon allergen provocation or by direct administration of IL-33. Eosinophilic airway inflammation is known to be associated with IL-5-dependent eosinophil development in the bone marrow, however, the source of IL-5 remains unclear. TH cells, ILC2s and CD34(+) progenitors have been proposed to be involved in this process, therefore, we investigated whether these cells are taking part in eosinophilopoiesis by producing IL-5 locally in the bone marrow in IL-33-driven inflammation...
September 16, 2017: Immunology
https://www.readbyqxmd.com/read/28921473/the-development-and-diversity-of-ilcs-nk-cells-and-their-relevance-in-health-and-diseases
#5
Yuxia Zhang, Bing Huang
Next to T and B cells, natural killer (NK) cells are the third largest lymphocyte population. They are recently re-categorized as innate lymphocytes (ILCs), which also include ILC1, ILC2, ILC3, and the lymphoid tissue inducer (LTi) cells. Both NK cells and ILC1 cells are designated as group 1 ILCs because they secrete interferon-γ (IFN-γ) and tumor necrosis factor (TNF). However, in contrast to ILC1 and all other ILCs, NK cells possess potent cytolytic functions that resemble cytotoxic T lymphocytes (CTL)...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/28917723/increased-innate-type-2-immune-response-in-house-dust-mite-allergic-patients-with-allergic-rhinitis
#6
Hua Zhong, Xing-Liang Fan, Qiu-Ning Yu, Zi-Li Qin, Dong Chen, Rui Xu, De-Hua Chen, Zhi-Bin Lin, Weiping Wen, Qing-Ling Fu
Group 2 innate lymphoid cells (ILC2s) are essential in initiating and driving allergic immune responses. However, there were inconsistent findings of the ILC2 levels in allergic rhinitis (AR) patients. This study investigated the ILC2 levels in the peripheral blood of house dust mite (HDM)-allergic AR patients and their ability to secrete type 2 cytokines. The levels of ILC2s with phenotypic ILC2 characteristics were increased in the HDM-AR patients. The AR patients' symptom score and IL-13 levels were positively associated with the ILC2s in HDM-AR patients...
September 13, 2017: Clinical Immunology: the Official Journal of the Clinical Immunology Society
https://www.readbyqxmd.com/read/28915080/weight-adjusted-intravenous-reslizumab-in-severe-asthma-with-inadequate-response-to-fixed-dose-subcutaneous-mepolizumab
#7
Manali Mukherjee, Fernando Aleman Paramo, Melanie Kjarsgaard, Brittany Salter, Gayatri Nair, Nicola LaVigne, Katherine Radford, Roma Sehmi, Parameswaran Nair
BACKGROUND: Clinical benefits of fixed-dose 100 mg subcutaneous (SC) mepolizumab in prednisone-dependent patients are modest when sputum eosinophilia is not adequately controlled. This study compared treatment response of weight-adjusted intravenous (IV) Reslizumab in patients previously treated with 100 mg SC Mepolizumab. METHOD: 10 prednisone-dependent asthmatics (sputum eosinophils >3% and blood eosinophils > 300cells/μL), who had previously received Mepolizumab (100 mg SC Q4W) for at least 1 year, received two infusions of placebo (Q4W) followed by 4 infusions of 3...
September 15, 2017: American Journal of Respiratory and Critical Care Medicine
https://www.readbyqxmd.com/read/28912783/sex-differences-in-asthma-a-key-role-of-androgen-signaling-in-group-2-innate-lymphoid-cells
#8
REVIEW
Sophie Laffont, Eve Blanquart, Jean-Charles Guéry
Infectious diseases, autoimmune diseases, and also allergy differentially affect women and men. In general, women develop strongest immune responses and thus the proportion of infected individuals and the severity of many viral, bacterial, or parasitic infections are increased in men. However, heightened immunity in women makes them more susceptible than men to autoimmunity and allergy. While sex differences in immunity are well documented, little is known about the cellular and molecular mechanisms underlying these immunological differences, particularly in allergic asthma...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28912776/human-cd5-innate-lymphoid-cells-are-functionally-immature-and-their-development-from-cd34-progenitor-cells-is-regulated-by-id2
#9
Maho Nagasawa, Kristine Germar, Bianca Blom, Hergen Spits
Innate lymphoid cells (ILCs) have emerged as a key cell type involved in surveillance and maintenance of mucosal tissues. Mouse ILCs rely on the transcriptional regulator Inhibitor of DNA-binding protein 2 (Id2) for their development. Here, we show that Id2 also drives development of human ILC because forced expression of Id2 in human thymic progenitors blocked T cell commitment, upregulated CD161 and promyelocytic leukemia zinc finger (PLZF), and maintained CD127 expression, markers that are characteristic for human ILCs...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28902842/the-neuropeptide-nmu-amplifies-ilc2-driven-allergic-lung-inflammation
#10
Antonia Wallrapp, Samantha J Riesenfeld, Patrick R Burkett, Raja-Elie E Abdulnour, Jackson Nyman, Danielle Dionne, Matan Hofree, Michael S Cuoco, Christopher Rodman, Daneyal Farouq, Brian J Haas, Timothy L Tickle, John J Trombetta, Pankaj Baral, Christoph S N Klose, Tanel Mahlakõiv, David Artis, Orit Rozenblatt-Rosen, Isaac M Chiu, Bruce D Levy, Monika S Kowalczyk, Aviv Regev, Vijay K Kuchroo
Type 2 innate lymphoid cells (ILC2s) both contribute to mucosal homeostasis and initiate pathologic inflammation in allergic asthma. However, the signals that direct ILC2s to promote homeostasis versus inflammation are unclear. To identify such molecular cues, we profiled mouse lung-resident ILCs using single-cell RNA sequencing at steady state and after in vivo stimulation with the alarmin cytokines IL-25 and IL-33. ILC2s were transcriptionally heterogeneous after activation, with subpopulations distinguished by expression of proliferative, homeostatic and effector genes...
September 13, 2017: Nature
https://www.readbyqxmd.com/read/28898280/ilc2s-activated-by-il-25-promote-antigen-specific-th2-and-th9-functions-that-contribute-to-the-control-of-trichinella-spiralis-infection
#11
Pornpimon Angkasekwinai, Wichuda Sodthawon, Siranart Jeerawattanawart, Adithap Hansakon, Kovit Pattanapanyasat, Yui-Hsi Wang
IL-25, an IL-17 family cytokine, derived from epithelial cells was shown to regulate Th2- and Th9-type immune responses. We previously reported that IL-25 was important in promoting efficient protective immunity against T. spiralis infection; however, the cellular targets of IL-25 to elicit type-2 immunity during infection have not yet been addressed. Here, we investigated IL-25-responding cells and their involvement in mediating type-2 immune response during T. spiralis infection. ILC2 and CD4+ Th2 cells residing in the gastrointestinal tract of T...
2017: PloS One
https://www.readbyqxmd.com/read/28895020/role-of-type-2-innate-lymphoid-cells-in-allergic-diseases
#12
REVIEW
Lorenzo Cosmi, Francesco Liotta, Laura Maggi, Francesco Annunziato
PURPOSE OF REVIEW: The adaptive immune response orchestrated by type 2 T helper (Th2) lymphocytes, strictly cooperates with the innate response of group 2 innate lymphoid cells (ILC2), in the protection from helminths infection, as well as in the pathogenesis of allergic disease. The aim of this review is to explore the pathogenic role of ILC2 in different type 2-mediated disorders. RECENT FINDINGS: Recent studies have shown that epithelial cell-derived cytokines and their responding cells, ILC2, play a pathogenic role in bronchial asthma, chronic rhinosinusitis, and atopic dermatitis...
September 11, 2017: Current Allergy and Asthma Reports
https://www.readbyqxmd.com/read/28880992/innate-lymphoid-cells-at-the-interface-between-obesity-and-asthma
#13
REVIEW
Laetitia Everaere, Saliha Ait Yahia, Mélodie Bouté, Camille Audousset, Cécile Chenivesse, Anne Tsicopoulos
Obesity and asthma prevalence has dramatically and concomitantly increased over the last 25 years, and many epidemiological studies have highlighted obesity as an important risk factor for asthma. Although many studies have been performed, the underlying mechanisms remain poorly understood. Innate mechanisms have been involved in both diseases in particular through the recently described innate lymphoid cells (ILCs). ILCs are subdivided in three groups that are defined by their cytokine production and by their master transcription factor expression, in sharp correlation with their T helper counterparts...
September 7, 2017: Immunology
https://www.readbyqxmd.com/read/28878863/innate-lymphoid-cells-in-tissue-homeostasis-and-diseases
#14
REVIEW
Aline Ignacio, Cristiane Naffah Souza Breda, Niels Olsen Saraiva Camara
Innate lymphoid cells (ILCs) are the most recently discovered family of innate immune cells. They are a part of the innate immune system, but develop from the lymphoid lineage. They lack pattern-recognition receptors and rearranged receptors, and therefore cannot directly mediate antigen specific responses. The progenitors specifically associated with the ILCs lineage have been uncovered, enabling the distinction between ILCs and natural killer cells. Based on the requirement of specific transcription factors and their patterns of cytokine production, ILCs are categorized into three subsets (ILC1, ILC2 and ILC3)...
August 18, 2017: World Journal of Hepatology
https://www.readbyqxmd.com/read/28878123/the-r213g-polymorphism-in-sod3-protects-against-allergic-airway-inflammation
#15
Rohit Gaurav, Jason T Varasteh, Michael R Weaver, Sean R Jacobson, Laura Hernandez-Lagunas, Qing Liu, Eva Nozik-Grayck, Hong Wei Chu, Rafeul Alam, Børge G Nordestgaard, Camilla J Kobylecki, Shoaib Afzal, Geoffrey L Chupp, Russell P Bowler
Oxidative stress is important in the pathogenesis of allergic asthma. Extracellular superoxide dismutase (EC-SOD; SOD3) is the major antioxidant in lungs, but its role in allergic asthma is unknown. Here we report that asthmatics have increased SOD3 transcript levels in sputum and that a single nucleotide polymorphism (SNP) in SOD3 (R213G; rs1799895) changes lung distribution of EC-SOD, and decreases likelihood of asthma-related symptoms. Knockin mice analogous to the human R213G SNP had lower airway hyperresponsiveness, inflammation, and mucus hypersecretion with decreased interleukin-33 (IL-33) in bronchoalveolar lavage fluid and reduced type II innate lymphoid cells (ILC2s) in lungs...
September 7, 2017: JCI Insight
https://www.readbyqxmd.com/read/28869974/neuronal-regulation-of-type-2-innate-lymphoid-cells-via-neuromedin-u
#16
Vânia Cardoso, Julie Chesné, Hélder Ribeiro, Bethania García-Cassani, Tânia Carvalho, Tiffany Bouchery, Kathleen Shah, Nuno L Barbosa-Morais, Nicola Harris, Henrique Veiga-Fernandes
Group 2 innate lymphoid cells (ILC2s) regulate inflammation, tissue repair and metabolic homeostasis, and are activated by host-derived cytokines and alarmins. Discrete subsets of immune cells integrate nervous system cues, but it remains unclear whether neuron-derived signals control ILC2s. Here we show that neuromedin U (NMU) in mice is a fast and potent regulator of type 2 innate immunity in the context of a functional neuron-ILC2 unit. We found that ILC2s selectively express neuromedin U receptor 1 (Nmur1), and mucosal neurons express NMU...
September 14, 2017: Nature
https://www.readbyqxmd.com/read/28869965/the-neuropeptide-neuromedin-u-stimulates-innate-lymphoid-cells-and-type-2-inflammation
#17
Christoph S N Klose, Tanel Mahlakõiv, Jesper B Moeller, Lucille C Rankin, Anne-Laure Flamar, Hiroki Kabata, Laurel A Monticelli, Saya Moriyama, Gregory Garbès Putzel, Nikolai Rakhilin, Xiling Shen, Evi Kostenis, Gabriele M König, Takashi Senda, Dustin Carpenter, Donna L Farber, David Artis
The type 2 cytokines interleukin (IL)-4, IL-5, IL-9 and IL-13 have important roles in stimulating innate and adaptive immune responses that are required for resistance to helminth infection, promotion of allergic inflammation, metabolic homeostasis and tissue repair. Group 2 innate lymphoid cells (ILC2s) produce type 2 cytokines, and although advances have been made in understanding the cytokine milieu that promotes ILC2 responses, how ILC2 responses are regulated by other stimuli remains poorly understood...
September 14, 2017: Nature
https://www.readbyqxmd.com/read/28863833/allergic-diseases-from-bench-to-clinic-contribution-of-the-discovery-of-interleukin-5
#18
REVIEW
Tsutomu Yanagibashi, Mitsuo Satoh, Yoshinori Nagai, Masamichi Koike, Kiyoshi Takatsu
T helper 2 cells produce a number of cytokines including inteleukin (IL)-5, IL-4 and IL-13. Group 2 innate lymphoid cells (ILC2s) also produce IL-5 under sterile conditions. IL-5 is interdigitating homodimeric glycoprotein and a member of the four α helical bundle motifs conserved among hematopoietic cytokines. IL-5 exerts its effects on target cells via IL-5 receptor (IL-5R), composed of an IL-5R α and βc subunit. The membrane proximal proline-rich motif of the cytoplasmic domain of both IL-5R α and βc subunits is essential for IL-5 signal transduction...
October 2017: Cytokine
https://www.readbyqxmd.com/read/28861078/increased-innate-lymphoid-cells-in-periodontal-tissue-of-the-murine-model-of-periodontitis-the-role-of-amp-activated-protein-kinase-and-relevance-for-the-human-condition
#19
Xu Qin, Md Nasrul Hoda, Cristiano Susin, Julie N Wheeler, Brendan Marshall, Libby Perry, Nancy Saad, Lin Yin, Ranya Elsayed, Mohammed Elsalanty, Rafik Abdelsayed, Jack C Yu, Krishnan M Dhandapani, Omid Akbari, Mahmood S Mozaffari, Babak Baban
Innate lymphoid cells (ILCs) are master regulators of immune and inflammatory responses, but their own regulatory mechanisms and functional roles of their subtypes (i.e., ILC1s-ILC3s) remain largely unresolved. Interestingly, AMP-activated protein kinase (AMPK), influences inflammatory responses, but its role in modulation of ILCs is not known. Periodontitis is a prevalent disorder with impairment of immune and inflammatory responses contributing importantly to its pathogenesis; however, neither the role of ILCs nor AMPK has been explored in this condition...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28855579/expression-of-il-33-in-ocular-surface-epithelium-induces-atopic-keratoconjunctivitis-with-activation-of-group-2-innate-lymphoid-cells-in-mice
#20
Yasutomo Imai, Yuka Hosotani, Hiroto Ishikawa, Koubun Yasuda, Makoto Nagai, Orie Jitsukawa, Fumi Gomi, Kenji Nakanishi, Tomohiro Yoshimoto, Takahiro Nakamura, Kiyofumi Yamanishi
In a transgenic mouse line hK14mIL33tg, with the expression of interleukin-33 (IL-33) driven by a keratin 14 promoter, keratoconjunctivitis developed spontaneously between 18 and 22 weeks of age under specific-pathogen-free conditions. These mice showed blepharitis and corneal impairments, and the histology revealed epithelial thickening in the conjunctiva and the cornea with infiltration of eosinophils, mast cells and basophils. IL-5, IL-13 and CCL11 were abundant in lacrimal fluid in the mice, and the gene expressions of IL-4, IL-5, IL-13, IL-33, Prg2 and Mmcp8 were significantly increased in the cornea...
August 30, 2017: Scientific Reports
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