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Innate lymphoid type 2 cells

Corinne Cayrol, Anais Duval, Pauline Schmitt, Stephane Roga, Mylène Camus, Alexandre Stella, Odile Burlet-Schiltz, Anne Gonzalez-de-Peredo, Jean-Philippe Girard
Allergic inflammation has crucial roles in allergic diseases such as asthma. It is therefore important to understand why and how the immune system responds to allergens. Here we found that full-length interleukin 33 (IL-33FL ), an alarmin cytokine with critical roles in type 2 immunity and asthma, functioned as a protease sensor that detected proteolytic activities associated with various environmental allergens across four kingdoms, including fungi, house dust mites, bacteria and pollens. When exposed to allergen proteases, IL-33FL was rapidly cleaved in its central 'sensor' domain, which led to activation of the production of type 2 cytokines in group 2 innate lymphoid cells...
March 19, 2018: Nature Immunology
Xing He, Jun Xie, Yange Wang, Xiaobin Fan, Qin Su, Yue Sun, Nanhang Lei, Dongmei Zhang, Guangping Gao, Weiqing Pan
The type 2 immune response is the central mechanism of disease progression in schistosomiasis, but the signals that induce it after infection remain elusive. Aberrant microRNA (miRNA) expression is a hallmark of human diseases including schistosomiasis, and targeting the deregulated miRNA can mitigate disease outcomes. Here, we demonstrate that efficient and sustained elevation of miR-203-3p in liver tissues, using the highly hepatotropic recombinant adeno-associated virus serotype 8 (rAAV8), protects mice against lethal schistosome infection by alleviating hepatic fibrosis...
March 19, 2018: PLoS Pathogens
Zhaodong Li, Ludovica F Buttó, Kristine-Anne Buela, Li-Guo Jia, Minh Lam, John D Ward, Theresa T Pizarro, Fabio Cominelli
Death receptor 3 (DR3), a member of the tumor necrosis factor receptor (TNFR) superfamily, has been implicated in regulating T-helper type-1 (TH 1), type-2 (TH 2), and type-17 (TH 17) responses as well as regulatory T cell (Treg ) and innate lymphoid cell (ILC) functions during immune-mediated diseases. However, the role of DR3 in controlling lymphocyte functions in inflammatory bowel disease (IBD) is not fully understood. Recent studies have shown that activation of DR3 signaling modulates Treg expansion suggesting that stimulation of DR3 represents a potential therapeutic target in human inflammatory diseases, including Crohn's disease (CD)...
2018: Frontiers in Immunology
David A Rafei-Shamsabadi, Saskia van de Poel, Britta Dorn, Stefanie Kunz, Stefan F Martin, Christoph S N Klose, Sebastian J Arnold, Yakup Tanriver, Karolina Ebert, Andreas Diefenbach, Timotheus Y F Halim, Andrew N J McKenzie, Thilo Jakob
Allergic contact dermatitis and its animal model, contact hypersensitivity (CHS), are T cell-mediated inflammatory skin diseases that require activation of the innate immune system. Here we investigate the role of innate lymphoid cells (ILCs) during the elicitation phase of TNCB-induced CHS using EomesGfp/+ x Rorc(γt)-CreTg x Rosa26RYfp/+ reporter mice. Ear swelling responses, cutaneous ILC numbers and cytokine production were determined at different time points. Functional analyses were performed in a CD90...
March 8, 2018: Journal of Investigative Dermatology
Christina Li-Ping Thio, Po-Yu Chi, Alan Chuan-Ying Lai, Ya-Jen Chang
BACKGROUND: Allergic asthma is characterized airway hyperreactivity (AHR) and inflammation driven by aberrant TH 2 response. Type 2 innate lymphoid cells (ILC2s) are a critical source of TH 2 cytokines IL-5 and IL-13 which promote acute asthma exacerbation. Short chain fatty acids (SCFAs) have been shown to attenuate T cell-mediated allergic airway inflammation. Their role in the regulation of ILC2-driven AHR and lung inflammation, however, remains unknown. OBJECTIVE: We investigated the immunomodulatory role of SCFAs in the regulation of ILC2-induced AHR and airway inflammation and delineated the mechanism involved...
March 6, 2018: Journal of Allergy and Clinical Immunology
Hajime Suto, Aya Nambu, Hideaki Morita, Sachiko Yamaguchi, Takafumi Numata, Takamichi Yoshizaki, Eri Shimura, Ken Arae, Yousuke Asada, Kenichiro Motomura, Mari Kaneko, Takaya Abe, Akira Matsuda, Yoichiro Iwakura, Ko Okumura, Hirohisa Saito, Kenji Matsumoto, Katsuko Sudo, Susumu Nakae
BACKGROUND: As well as thymic stromal lymphopoietin (TSLP) and IL-33, IL-25 is known to induce Th2 cytokine production by various cell types-including Th2 cells, Th9 cells, invariant NKT cells and group 2 innate lymphoid cells-involved in Th2-type immune responses. Since both Th2-type and Th17-type cells/cytokines are crucial for contact hypersensitivity (CHS), IL-25 may contribute to this by enhancing Th2-type immune responses. However, the precise role of IL-25 in the pathogenesis of FITC-induced CHS is poorly understood...
March 6, 2018: Journal of Allergy and Clinical Immunology
Nidhi Malhotra, Juan Manuel Leyva-Castillo, Unmesh Jadhav, Olga Barreiro, Christy Kam, Nicholas K O'Neill, Francoise Meylan, Pierre Chambon, Ulrich H von Andrian, Richard M Siegel, Eddie C Wang, Ramesh Shivdasani, Raif S Geha
Atopic dermatitis is an allergic inflammatory skin disease characterized by the production of the type 2 cytokines in the skin by type 2 innate lymphoid cells (ILC2s) and T helper 2 (TH 2) cells, and tissue eosinophilia. Using two distinct mouse models of atopic dermatitis, we show that expression of retinoid-related orphan receptor α (RORα) in skin-resident T regulatory cells (Tregs ) is important for restraining allergic skin inflammation. In both models, targeted deletion of RORα in mouse Tregs led to exaggerated eosinophilia driven by interleukin-5 (IL-5) production by ILC2s and TH 2 cells...
March 2, 2018: Science Immunology
Saya Moriyama, Jonathan R Brestoff, Anne-Laure Flamar, Jesper B Moeller, Christoph S N Klose, Lucille C Rankin, Naomi A Yudanin, Laurel A Monticelli, Gregory Garbès Putzel, Hans-Reimer Rodewald, David Artis
The type 2 inflammatory response is induced by various environmental and infectious stimuli. Although recent studies identified group 2 innate lymphoid cells (ILC2s) as potent sources of type 2 cytokines, the molecular pathways controlling ILC2 responses are incompletely defined. Here we demonstrate that murine ILC2s express the β2 -adrenergic receptor (β2 AR) and colocalize with adrenergic neurons in the intestine. β2 AR deficiency resulted in exaggerated ILC2 responses and type 2 inflammation in intestinal and lung tissues...
March 2, 2018: Science
Martijn J Schuijs, Timotheus Y F Halim
Group 2 innate lymphoid cells (ILC2) are innate immune cells that respond rapidly to their environment through soluble inflammatory mediators and cell-to-cell interactions. As tissue-resident sentinels, ILC2 help orchestrate localized type 2 immune responses. These ILC2-driven type 2 responses are now recognized in diverse immune processes, different anatomical locations, and homeostatic or pathological settings. ILC2-derived cytokines and cell surface signaling molecules function as key regulators of innate and adaptive immunity...
March 1, 2018: Annals of the New York Academy of Sciences
Naina Gour, Stephane Lajoie, Ursula Smole, Marquitta White, Donglei Hu, Pagé Goddard, Scott Huntsman, Celeste Eng, Angel Mak, Sam Oh, Jung-Hyun Kim, Annu Sharma, Sophie Plante, Ikhlass Haj Salem, Yvonne Resch, Xiao Xiao, Nu Yao, Anju Singh, Susanne Vrtala, Jamila Chakir, Esteban G Burchard, Andrew P Lane, Marsha Wills-Karp
The key factors underlying the development of allergic diseases-the propensity for a minority of individuals to develop dysfunctional responses to harmless environmental molecules-remain undefined. We report a pathway of immune counter-regulation that suppresses the development of aeroallergy and shrimp-induced anaphylaxis. In mice, signaling through epithelially expressed dectin-1 suppresses the development of type 2 immune responses through inhibition of interleukin-33 (IL-33) secretion and the subsequent recruitment of IL-13-producing innate lymphoid cells...
February 23, 2018: Science Immunology
Audrey Baeyens, Susan R Schwab
In many contexts, innate lymphoid cells (ILCs) are primarily tissue resident. By contrast, in a recent issue of Science, Huang et al. (2018) show that inflammatory type 2 ILCs migrate from the intestine to the lungs and that this movement is guided by sphingosine-1-phosphate receptors.
February 20, 2018: Immunity
Sayantani B Sindher, Andrew Long, Swati Acharya, Vanitha Sampath, Kari C Nadeau
The incidence of allergic conditions has continued to rise over the past several decades, with a growing body of research dedicated toward the treatment of such conditions. By driving a complex range of changes in the underlying immune response, immunotherapy is the only therapy that modulates the immune system with long-term effects and is presently utilized for the treatment of several atopic conditions. Recent efforts have focused on identifying biomarkers associated with these changes that may be of use in predicting patients with the highest likelihood of positive clinical outcomes during allergen immunotherapy (AIT), providing guidance regarding AIT discontinuation, and predicting symptomatic relapse and the need for booster AIT after therapy...
February 17, 2018: Clinical Reviews in Allergy & Immunology
Qian Li, Dulei Li, Xian Zhang, Qingqing Wan, Wen Zhang, Mingke Zheng, Le Zou, Chris Elly, Jee H Lee, Yun-Cai Liu
Group 2 innate lymphoid cells (ILC2s) are a specialized subset of lymphoid effector cells that are critically involved in allergic responses; however, the mechanisms of their regulation remain unclear. We report that conditional deletion of the E3 ubiquitin ligase VHL in innate lymphoid progenitors minimally affected early-stage bone marrow ILC2s but caused a selective and intrinsic decrease in mature ILC2 numbers in peripheral non-lymphoid tissues, resulting in reduced type 2 immune responses. VHL deficiency caused the accumulation of hypoxia-inducible factor 1α (HIF1α) and attenuated interleukin-33 (IL-33) receptor ST2 expression, which was rectified by HIF1α ablation or inhibition...
February 6, 2018: Immunity
Qing Miao, Yan Wang, Yong-Ge Liu, Yi-Xin Ren, Hui Guan, Zhen Li, Wei Xu, Li Xiang
Background: Group 2 innate lymphoid cells (ILC2s) are a newly identified cell population with the potent capability to produce Th2-type cytokines in a non-antigen specific manner. Previous study demonstrated that enhanced circulating ILC2s in cat-allergic patient after experimental allergen challenge, whereas the effects of natural allergen exposure on peripheral ILC2s are still unclear. We therefore examined the variations in circulating ILC2s among asthmatic patients sensitized to different allergens in- and outside- pollen season...
2018: Allergy, Asthma, and Clinical Immunology
Iryna Saranchova, Jeffrey Han, Rysa Zaman, Hitesh Arora, Hui Huang, Franz Fenninger, Kyung Bok Choi, Lonna Munro, Cheryl G Pfeifer, Ian Welch, Fumio Takei, Wilfred A Jefferies
Type 2 innate lymphoid cells (ILC2) potentiate immune responses, however, their role in mediating adaptive immunity in cancer has not been assessed. Here, we report that mice genetically lacking ILC2s have significantly increased tumour growth rates and conspicuously higher frequency of circulating tumour cells (CTCs) and resulting metastasis to distal organs. Our data support the model that IL-33 dependent tumour-infiltrating ILC2s are mobilized from the lungs and other tissues through chemoattraction to enter tumours, and subsequently mediate tumour immune-surveillance by cooperating with dendritic cells to promote adaptive cytolytic T cell responses...
February 13, 2018: Scientific Reports
Abdulrahman M Saadalla, Abu Osman, Michael F Gurish, Kristen L Dennis, Nichole R Blatner, Abdulmohammad Pezeshki, Kelly M McNagny, Hilde Cheroutre, Fotini Gounari, Khashayarsha Khazaie
Mast cells (MCs) are tissue resident sentinels that mature and orchestrate inflammation in response to infection and allergy. While they are also frequently observed in tumors, the contribution of MCs to carcinogenesis remains unclear. Here, we show that sequential oncogenic events in gut epithelia expand different types of MCs in a temporal-, spatial-, and cytokine-dependent manner. The first wave of MCs expands focally in benign adenomatous polyps, which have elevated levels of IL-10, IL-13, and IL-33, and are rich in type-2 innate lymphoid cells (ILC2s)...
February 13, 2018: Proceedings of the National Academy of Sciences of the United States of America
Hui-Ying Tung, Evan Li, Cameron Landers, An Nguyen, Farrah Kheradmand, J Morgan Knight, David B Corry
Allergic asthma is a heterogeneous disorder that defies a unanimously acceptable definition, but is generally recognized through its highly characteristic clinical expression of dyspnea and cough accompanied by clinical data that document reversible or exaggerated airway constriction and obstruction. The generally rising prevalence of asthma in highly industrialized societies despite significant therapeutic advances suggests that the fundamental cause(s) of asthma remain poorly understood. Detailed analyses of both the indoor (built) and outdoor environments continue to support the concept that not only inhaled particulates, especially carbon-based particulate pollution, pollens, and fungal elements, but also many noxious gases and chemicals, especially biologically derived byproducts such as proteinases, are essential to asthma pathogenesis...
February 2018: Seminars in Respiratory and Critical Care Medicine
Yuejin Liang, Panpan Yi, Denley Ming Kee Yuan, Zuliang Jie, Zakari Kwota, Lynn Soong, Yingzi Cong, Jiaren Sun
Viral hepatitis is still a public health problem affecting several million people around the world. Neutrophils are polymorphonuclear cells that have a critical role in antibacterial infection. However, the role of neutrophils in viral infection is not fully understood. By using a mouse model of lymphocytic choriomeningitis virus infection-induced viral hepatitis, we observed increased neutrophil recruitment in the liver accompanied by enhanced CD8+ T-cell responses. Liver neutrophils expressed high levels of immunomodulatory cytokines, such as C-X-C chemokine ligand 2, arginase-1, inducible nitric oxide synthase and interleukin (IL)-10, demonstrating immunosuppressive properties...
February 5, 2018: Cellular & Molecular Immunology
Koichi Hirose, Takashi Ito, Hiroshi Nakajima
Asthma is a chronic inflammatory disease of the airways that is characterized by eosinophilic inflammation, mucus hypersecretion and airway remodeling that leads to airway obstruction. Although these pathognomonic features of asthma are primarily mediated by allergen-specific T helper type 2 cells (Th2 cells) and their cytokines, recent studies have revealed critical roles of lung epithelial cells in the pathogenesis of asthma. Lung epithelial cells not only form physical barriers by covering the surfaces of the airways but also sense inhaled allergens and initiate communication between the environment and the immune system...
January 31, 2018: International Immunology
Abigail E Russi, Mark E Ebel, Yuchen Yang, Melissa A Brown
The cellular and molecular basis of sex-dimorphic autoimmune diseases, such as the CNS demyelinating disease multiple sclerosis (MS), remains unclear. Our studies in the SJL mouse model of MS, experimental autoimmune encephalomyelitis (EAE), reveal that sex-determined differences in Il33 expression by innate immune cells in response to myelin peptide immunization regulate EAE susceptibility. IL-33 is selectively induced in PLP139-151 -immunized males and activates type 2 innate lymphoid cells (ILC2s), cells that promote and sustain a nonpathogenic Th2 myelin-specific response...
February 13, 2018: Proceedings of the National Academy of Sciences of the United States of America
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