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Pulmonary – Treatable traits
Published in Vibeke Backer, Peter G. Gibson, Ian D. Pavord, The Asthmas, 2023
Vibeke Backer, Peter G. Gibson, Ian D. Pavord
Interestingly, around 50% of patients with severe asthma and eosinophilic inflammation are not atopic and many have normal serum IgE. This counterintuitive finding implies that the pathology can be induced independently of exogenous allergens. This may become a dominant mechanism in more severe asthma which typically persists independent of allergen exposure. A newly recognised class of cells called type-2 innate lymphoid cells (ILC2) might drive persistent eosinophilic inflammation. ILC2s produce large amounts of IL-5 and IL-13 but less IL-4, making them an attractive candidate for orchestrating the immune response in patients with non-atopic eosinophilic airway inflammation. The current paradigm for the role of ILC2s is that disruption of the epithelial barrier by an external trigger, for example, a virus, causes epithelial damage and enhances production of IL-25, IL-33 and thymic stromal lymphopoietin (TSLP) by epithelial cells (Figure 2.7). These cytokines cause ILC2 activation in the tissue and release of the type-2 cytokines. Production of prostaglandin D2 and LTE4 by recruited and activated eosinophils and mast cells might then enhance responsiveness of ILC2 cells leading to a perpetuating cycle (Figure 2.7).
Basics of Allergy
Published in Pudupakkam K Vedanthan, Harold S Nelson, Shripad N Agashe, PA Mahesh, Rohit Katial, Textbook of Allergy for the Clinician, 2021
Rafeul Alam, Dipa K Sheth, Magdalena M Gorska
Recent studies have identified a distinct population of innate lymphoid cells (Klose and Artis 2016, Mjosberg et al. 2011). These ILCs are analogous to T helper cells in their function. ILC1, ILC2 and ILC3 have a cytokine profile that is similar to that of Th1, Th2 and Th17. Although their frequency is low compared to T helper cells, ILCs produce much higher quantities of effector cytokines (e.g., IL5 and IL13 production by ILC2s) and significantly contribute to the pathogenesis of inflammatory diseases and host defense.
Immunologic responses to various forms of allergen immunotherapy
Published in Richard F. Lockey, Dennis K. Ledford, Allergens and Allergen Immunotherapy, 2020
Umit Murat Sahiner, Mohamed H. Shamji, Sakura Sato, Ozge Soyer, Stephen J. Till, Motohiro Ebisawa, Mübeccel Akdis, Stephen R. Durham
Innate lymphoid cells (ILCs) are defined as a novel subset of lymphoid cells that lack antigen-specific receptors and are divided into three different subgroups. ILC2s are under the control of transcription factor GATA-3, and once activated by epithelium-derived IL-25, IL-33, and thymic stromal lymphopoietin (TSLP), they produce type 2 cytokines IL-4, IL-5, and IL-13 [5,6]. ILC2s represent an important alternative source of type 2 cytokines and are likely to increase and maintain the local allergic inflammation. Recently, the role of ILC2s is defined in several diseases, such as allergic airway inflammation [7,8], allergic rhinitis [9], atopic dermatitis [10], and eosinophilic esophagitis [11].
Targeting interleukin 4 and interleukin 13: a novel therapeutic approach in bullous pemphigoid
Published in Annals of Medicine, 2023
Fangyuan Chen, Yiman Wang, Xinyi Chen, Nan Yang, Li Li
ILC2 cells are innate lymphoid cells that can produce large amounts of type 2 cytokines. Considerable research has been conducted regarding the role of ILC2s in asthma. In mouse studies regarding the pathogenesis of asthma, it was revealed that ILC2s are major sources of IL-5 and IL-13 [63]. Interestingly, the authors found that when patients with asthma were treated with corticosteroids, cytokines produced by Th2 cells decreased but cytokines of ILC2s were not suppressed. These findings may explain the corticosteroid resistance in asthma patients [63]. The study from Bartemes et al. revealed that ILC2s were abundant in the peripheral blood of patients with allergic asthma, and ILC2s could be recruited to mucosal tissues through peripheral blood circulation. Furthermore, ILC2s also have the ability to induce eosinophil acumination in tissue [64]. However, allergic rhinitis, another Th2-dominant immune response disease, did not show an increase in ILC2s [64]. In skin diseases, ILC2s have been proven to be involved in AD [65], but there has been no research concerning ILC2s in BP. Although ILC2s may not able to be markers for Th2 immune response, further studies are needed to fully elucidate their role.
Airway smooth muscle in contractility and remodeling of asthma: potential drug target mechanisms
Published in Expert Opinion on Therapeutic Targets, 2023
Latifa Khalfaoui, Christina M. Pabelick
Non-allergic eosinophilic asthma mostly develops in the absence of an allergen-dependent activation of TH2 lymphocytes, and patients with non-allergic eosinophilic asthma often do not respond to treatment with inhaled corticosteroids [11]. ILC2s (type 2 innate lymphoid cells) have been implicated in non-atopic eosinophilic asthma. Recent research showed that these cells are key mediators in the production of TH2-associated cytokines including IL-5 and IL-13 upon stimulation with TSLP and IL-33 [38]. There is evidence that ILC2s play a significant role in the pathogenesis of asthma, as evidenced by the increase of ILC2s in asthmatic peripheral blood [39], and sputum [40]. It is believed that these cells are critically involved in the development of type 2-mediated airway inflammation during viral-induced asthma exacerbations [41]. In addition, these cells have been shown to promote AHR in mice that was prevented by inhibition of vascular endothelial growth factor (VEGF) signaling [42].
A RAS inhibitor reduces allergic airway remodeling via regulating IL-33-derived type 2 innate lymphoid cells
Published in Experimental Lung Research, 2021
Toshifumi Tezuka, Masahiko Azuma, Hirohisa Ogawa, Mayo Kondo, Hisanori Uehara, Yoshinori Aono, Masaki Hanibuchi, Yasuhiko Nishioka
IL-33 stimulates ILC2s to produce the type 2 cytokines IL-5 and IL-13. ILC2s from bronchoalveolar lavage fluid of asthmatics were resistant to dexamethasone.8 House dust mites induced airway hyperresponsiveness, goblet cell hyperplasia and peribronchiolar collagen deposition in a mouse model, but these changes were not induced in ST2-/- mice.7–9 IL-33 expression is significantly increased in submucosal inflammatory cells in severe asthmatic patients, and is associated with corticosteroid resistance. The number of activated ILC2 was increased in the airways of patients with severe asthma.10 ILC2s could contribute to corticosteroid resistance in asthmatic patients. Corticosteroids block IL-33-dependent proliferation and type-2 cytokine production in ILC2s, but IL-2, IL-7, IL-9 and TSLP decrease these corticosteroid sensitivities.3