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Lauriane Galle-Treger, Yuzo Suzuki, Nisheel Patel, Ishwarya Sankaranarayanan, Jennifer L Aron, Hadi Maazi, Lin Chen, Omid Akbari
Allergic asthma is a complex and chronic inflammatory disorder that is associated with airway hyperreactivity (AHR) and driven by Th2 cytokine secretion. Type 2 innate lymphoid cells (ILC2s) produce large amounts of Th2 cytokines and contribute to the development of AHR. Here, we show that ILC2s express the α7-nicotinic acetylcholine receptor (α7nAChR), which is thought to have an anti-inflammatory role in several inflammatory diseases. We show that engagement of a specific agonist with α7nAChR on ILC2s reduces ILC2 effector function and represses ILC2-dependent AHR, while decreasing expression of ILC2 key transcription factor GATA-3 and critical inflammatory modulator NF-κB, and reducing phosphorylation of upstream kinase IKKα/β...
October 18, 2016: Nature Communications
Steven J Van Dyken, Jesse C Nussbaum, Jinwoo Lee, Ari B Molofsky, Hong-Erh Liang, Joshua L Pollack, Rachel E Gate, Genevieve E Haliburton, Chun J Ye, Alexander Marson, David J Erle, Richard M Locksley
Group 2 innate lymphoid cells (ILC2s) and CD4(+) type 2 helper T cells (TH2 cells) are defined by their similar effector cytokines, which together mediate the features of allergic immunity. We found that tissue ILC2s and TH2 cells differentiated independently but shared overlapping effector function programs that were mediated by exposure to the tissue-derived cytokines interleukin 25 (IL-25), IL-33 and thymic stromal lymphopoietin (TSLP). Loss of these three tissue signals did not affect lymph node priming, but abrogated the terminal differentiation of effector TH2 cells and adaptive lung inflammation in a T cell-intrinsic manner...
October 17, 2016: Nature Immunology
Yong Yu, Jason C H Tsang, Cui Wang, Simon Clare, Juexuan Wang, Xi Chen, Cordelia Brandt, Leanne Kane, Lia S Campos, Liming Lu, Gabrielle T Belz, Andrew N J McKenzie, Sarah A Teichmann, Gordon Dougan, Pentao Liu
Innate lymphoid cells (ILCs) functionally resemble T lymphocytes in cytotoxicity and cytokine production but lack antigen-specific receptors, and are important regulators in immune response and tissue homeostasis(1, 2). ILCs are generated from common lymphoid progenitors (CLPs), which are subsequently committed to innate lymphoid lineages in the α lymphoid progenitor (αLP), early innate lymphoid progenitor (EILP), common helper innate lymphoid progenitor (CHILP) and innate lymphoid cell progenitor (ILCP) compartments(3, 4, 5, 6, 7, 8)...
September 29, 2016: Nature
Fahima Madouri, Pauline Chenuet, Chloé Beuraud, Louis Fauconnier, Tiffany Marchiol, Nathalie Rouxel, Aurélie Ledru, Margaux Gallerand, Vincent Lombardi, Laurent Mascarell, Quentin Marquant, Lionel Apetoh, François Erard, Marc Le Bert, Fabrice Trovero, Valérie F J Quesniaux, Bernhard Ryffel, Dieudonnée Togbe
BACKGROUND: Protein Kinase C theta (PKC-θ), a serine/threonine kinase is involved in T helper 2 (Th2) cell activation and proliferation. Innate lymphoid cells 2 (ILC2) resemble Th2 cells; produce the Th2 cytokines IL-5 and IL-13, but lack antigen specific receptors. The mechanism by which PKC-θ drives innate immune cells to instruct Th2 responses in allergic lung inflammation remains unknown. OBJECTIVES: We hypothesized that PKC-θ contributes to ILC2 activation and may be necessary for ILC2 to instruct Th2 response...
October 13, 2016: Journal of Allergy and Clinical Immunology
H Vroman, I M Bergen, B W S Li, J A C van Hulst, M Lukkes, D van Uden, R W Hendriks, M Kool
BACKGROUND: Chronic exposure to environmental triggers, such as house dust mite (HDM), drives T helper 2 (Th2) cell-mediated asthma. Recent evidence has shown that B-T cell interaction, and in particular germinal center reactions and follicular T helper (Tfh) cells are required for the development of eosinophilic airway inflammation in HDM-driven models containing a sensitization and challenge phase. Whether B-T cell interactions are essential for pulmonary eosinophilic inflammation following chronic allergen provocation remains unknown...
October 15, 2016: Clinical and Experimental Allergy: Journal of the British Society for Allergy and Clinical Immunology
L Mascarell, S Airouche, N Berjont, C Gary, C Gueguen, G Fourcade, B Bellier, D Togbe, B Ryffel, D Klatzmann, V Baron-Bodo, P Moingeon
The complement subunit C1q was recently identified as a marker for monocyte-derived regulatory dendritic cells supporting the differentiation of interleukin (IL)-10-secreting CD4(+) T cells with a suppressive activity. Furthermore, C1q expression is upregulated in peripheral blood mononuclear cells of allergic patients in the course of successful allergen immunotherapy. Herein, we investigated a potential direct role of C1q in downregulating allergic inflammation. In mice with ovalbumin (OVA) or birch pollen (BP)-induced allergic asthma, C1q is as efficacious as dexamethasone to reduce both airway hyperresponsiveness (AHR), eosinophil, and ILC2 infiltrates in bronchoalveolar lavages, as well as allergen-specific T helper 2 cells in the lungs...
October 12, 2016: Mucosal Immunology
Diamanda Rigas, Gavin Lewis, Jennifer L Aron, Bowen Wang, Homayon Banie, Ishwarya Sankaranarayanan, Lauriane Galle-Treger, Hadi Maazi, Richard Lo, Gordon J Freeman, Arlene H Sharpe, Pejman Soroosh, Omid Akbari
BACKGROUND: Atopic diseases including asthma exacerbate type 2 immune responses and involve a number of immune cell types, including regulatory T cells (Tregs) and the emerging group 2 innate lymphoid cells (ILC2s). While ILC2s are potent producers of type 2 cytokines, the regulation of ILC2 activation and function is not well understood. OBJECTIVE: In the present study, we evaluate for the first time how Tregs interact with pulmonary ILC2s and control their function...
October 4, 2016: Journal of Allergy and Clinical Immunology
Tao Huang, Meredith Hazen, Yonglei Shang, Meijuan Zhou, Xiumin Wu, Donghong Yan, Zhonghua Lin, Margaret Solon, Elizabeth Luis, Hai Ngu, Yongchang Shi, Arna Katewa, David F Choy, Nandhini Ramamoorthi, Erick R Castellanos, Mercedesz Balazs, Min Xu, Wyne P Lee, Marissa L Matsumoto, Jian Payandeh, Joseph R Arron, Jo-Anne Hongo, Jianyong Wang, Isidro Hötzel, Cary D Austin, Karin Reif
Eosinophilic inflammation and Th2 cytokine production are central to the pathogenesis of asthma. Agents that target either eosinophils or single Th2 cytokines have shown benefits in subsets of biomarker-positive patients. More broadly effective treatment or disease-modifying effects may be achieved by eliminating more than one inflammatory stimulator. Here we present a strategy to concomitantly deplete Th2 T cells, eosinophils, basophils, and type-2 innate lymphoid cells (ILC2s) by generating monoclonal antibodies with enhanced effector function (19A2) that target CRTh2 present on all 4 cell types...
May 19, 2016: JCI Insight
Mingyuan Han, Jun Young Hong, Suraj Jaipalli, Charu Rajput, Jing Lei, Joanna L Hinde, Qiang Chen, Natalie M Hershenson, J Kelley Bentley, Marc B Hershenson
Early-life wheezing-associated infections with rhinovirus (RV) have been associated with asthma development in children. We have shown that RV infection of six day-old mice induces mucous metaplasia and airways hyperresponsiveness which is dependent on IL-13, IL-25 and type 2 innate lymphoid cells (ILC2s). Infection of immature mice fails to induce lung IFN-γ expression, in contrast to mature 8 week-old mice with a robust IFN-γ response, consistent with the notion that deficient IFN-γ production in immature mice permits RV-induced type 2 immune responses...
September 28, 2016: American Journal of Respiratory Cell and Molecular Biology
Jenny Mjösberg, Hergen Spits
Innate lymphoid cells (ILC) are increasingly acknowledged as important mediators of immune homeostasis and pathology. ILC act as early orchestrators on immunity, responding to epithelial-derived signals by expressing an array of cytokines and cell surface receptors, which shape subsequent immune responses. As such, ILC make up interesting therapeutic targets for several diseases. In allergy and asthma, group 2 ILC (ILC2) produce high amounts of IL-5 and IL-13, thereby contributing to type 2 mediated inflammation...
September 24, 2016: Journal of Allergy and Clinical Immunology
Ayako Matsuki, Hiroaki Takatori, Sohei Makita, Masaya Yokota, Tomohiro Tamachi, Akira Suto, Kotaro Suzuki, Koichi Hirose, Hiroshi Nakajima
BACKGROUND: Innate lymphoid cells (ILCs) are emerging subsets of immune cells that produce large amounts of cytokines upon cytokine and/or alarmin stimulation. Recent studies have shown that T-bet plays pivotal roles in the development of ILC3s and ILC1s; however, the roles of T-bet in lung ILC2s remain unknown. OBJECTIVE: To determine the role of T-bet in ILC2-mediated airway inflammation. METHODS: The expression of T-bet in lung ILCs (defined as Thy1...
September 23, 2016: Journal of Allergy and Clinical Immunology
Erika Simmerman, Xu Qin, Brendan Marshall, Libby Perry, Lei Cai, Tailing Wang, Jack Yu, Omid Akbari, Babak Baban
BACKGROUND: Cleft lip and palate reconstructions demonstrate significantly lower surgical site infection rates compared with clean-contaminated cases, prompting investigation into the pathophysiology causing this discrepancy. Recent studies have identified a new group of innate lymphocytes called innate lymphoid cells (ILCs), located in barrier surfaces of the skin, airways, and intestine. Our objectives were to explore for the first time the presence of ILCs in the vermillion of neonates and young children undergoing cleft lip reconstruction and characterize their composition by measuring the three classes of ILCs...
October 2016: Journal of Surgical Research
Maciej Chalubinski, Emilia Luczak, Katarzyna Wojdan, Paulina Gorzelak-Pabis, Marlena Broncel
The low-grade inflammation present in obese visceral adipose tissue impairs glucose metabolism, and contributes to the development of insulin resistance and weight gain. Immune processes occurring in response to the deposition of cholesterol within the vascular walls support atherosclerotic plaque growth and contribute to the cardiovascular complications. In both the obese adipose tissue and the atherosclerotic plaque, the Th1-type immune environment dominates over the Th2/Treg-type due to the overproduction of pro-inflammatory cytokines (IFN-γ, IL-6, TNF-α) and the deficiency of Th2-type processes and interleukins (IL-4, IL-5, IL-10, IL-13)...
September 16, 2016: Immunology Letters
Foo Yew Liew, Jean-Philippe Girard, Heth Roderick Turnquist
Interleukin-33 (IL-33) - a member of the IL-1 family - was originally described as an inducer of type 2 immune responses, activating T helper 2 (TH2) cells and mast cells. Now, evidence is accumulating that IL-33 also potently stimulates group 2 innate lymphoid cells (ILC2s), regulatory T (Treg) cells, TH1 cells, CD8(+) T cells and natural killer (NK) cells. This pleiotropic nature is reflected in the role of IL-33 in tissue and metabolic homeostasis, infection, inflammation, cancer and diseases of the central nervous system...
September 19, 2016: Nature Reviews. Immunology
Lucy H Jackson-Jones, Sheelagh M Duncan, Marlène S Magalhaes, Sharon M Campbell, Rick M Maizels, Henry J McSorley, Judith E Allen, Cécile Bénézech
Fat-associated lymphoid clusters (FALC) are inducible structures that support rapid innate-like B-cell immune responses in the serous cavities. Little is known about the physiological cues that activate FALCs in the pleural cavity and more generally the mechanisms controlling B-cell activation in FALCs. Here we show, using separate models of pleural nematode infection with Litomosoides sigmodontis and Altenaria alternata induced acute lung inflammation, that inflammation of the pleural cavity rapidly activates mediastinal and pericardial FALCs...
2016: Nature Communications
Laura Maggi, Gianni Montaini, Alessio Mazzoni, Beatrice Rossettini, Manuela Capone, Maria Caterina Rossi, Veronica Santarlasci, Francesco Liotta, Oliviero Rossi, Oreste Gallo, Raffaele De Palma, Enrico Maggi, Lorenzo Cosmi, Sergio Romagnani, Francesco Annunziato
BACKGROUND: Protection against helminths consists of adaptive responses by TH2 cells and innate responses by group 2 innate lymphoid cells (ILC2s), with these latter being well characterized in mice but less so in human subjects. OBJECTIVE: We sought to characterize human circulating ILC2s and compare their functional profile with that of autologous TH2 cells. METHODS: Circulating ILC2s and TH2 cells were isolated by means of fluorescence-activated cell sorting and magnetic cell sorting and expanded in vitro...
July 27, 2016: Journal of Allergy and Clinical Immunology
Ayako Ishimori, Norihiro Harada, Asako Chiba, Sonoko Harada, Kei Matsuno, Fumihiko Makino, Jun Ito, Shoichiro Ohta, Junya Ono, Ryo Atsuta, Kenji Izuhara, Kazuhisa Takahashi, Sachiko Miyake
BACKGROUND: A variety of innate subsets of lymphoid cells such as natural killer (NK) cells, several populations of innate lymphoid cells (ILCs), and mucosal-associated invariant T (MAIT) cells as innate-like T lymphocytes are involved in asthma and may have important effector functions in asthmatic immune responses. In the present study, we investigated whether NK cells, ILCs, and MAIT cells in the peripheral blood of patients with asthma would be associated with clinical asthma parameters...
August 26, 2016: Allergology International: Official Journal of the Japanese Society of Allergology
Jee-Boong Lee
Due to the increasing prevalence and number of life-threatening cases, food allergy has emerged as a major health concern. The classic immune response seen during food allergy is allergen-specific IgE sensitization and hypersensitivity reactions to foods occur in the effector phase with often severe and deleterious outcomes. Recent research has advanced understanding of the immunological mechanisms occurring during the effector phase of allergic reactions to ingested food. Therefore, this review will not only cover the mucosal immune system of the gastrointestinal tract and the immunological mechanisms underlying IgE-mediated food allergy, but will also introduce cells recently identified to have a role in the hypersensitivity reaction to food allergens...
August 2016: Immune Network
Rafiou Agoro, Julie Piotet-Morin, Jennifer Palomo, Chloé Michaudel, Solenne Vigne, Isabelle Maillet, Pauline Chenuet, Noëlline Guillou, Jessica Le Bérichel, Malgorzata Kisielow, Ulf Per Flodby, Marc Le Bert, Valérie Quesniaux, Matthias Muller, Franco Di Padova, Bernhard Ryffel, Cem Gabay, Aurélie Couturier-Maillard
Allergic asthma is characterized by a strong Th2 response with inflammatory cell recruitment and structural changes in the lung. Papain is a protease allergen disrupting the airway epithelium triggering a rapid inflammation with eosinophilia mediated by innate lymphoid cell activation (ILC2) and leading to a Th2 immune response. In this study, we focused on inflammatory responses to a single exposure to papain and showed that intranasal administration of papain results in the recruitment of inflammatory cells, including neutrophils and eosinophils with a rapid production of IL-1α, IL-1β, and IL-33...
August 28, 2016: European Journal of Immunology
Handong Zheng, Xing Zhang, Eliseo F Castillo, Yan Luo, Meilian Liu, Xuexian O Yang
Allergic asthma and obesity are the leading health problems in the world. Many studies have shown that obesity is a risk factor of development of asthma. However, the underlying mechanism has not been well established. In this study, we demonstrate that leptin, an adipokine elevated in obese individuals, promoted proliferation and survival of pro-allergic type 2 helper T cells and group 2 innate lymphoid cells and production of type 2 cytokines, which together contribute to allergic responses. Leptin activates mTORC1, MAPK, and STAT3 pathways in TH2 cells...
October 14, 2016: Journal of Biological Chemistry
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