Obesity May Provide Pro-ILC3 Development Inflammatory Environment in Asthmatic Children

Wu, Yue; Yue, Jiawei; Wu, Jun-Cheng; Zhou, Wei; Li, Dapeng; Ding, Kai; Barnie, Prince Amoah; Xu, Xu; Xu, Huaxi; Shi, Weifeng

doi:10.1155/2018/1628620

Cited by 20 publications

(13 citation statements)

References 45 publications

(47 reference statements)

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“…Besides the here described involvement of cytokines ( Table 1), mucosal immune cells, and bacteria in the ILC3-activating machinery, several other factors have been suggested to be crucial promotors of local ILC3 accumulation and function in humans, such as neurotransmitters, vitamin metabolites, and even lifestyle (e.g., obesity and cigarette smoking) (107,108,193,194). In the case of neurotransmitters, vagus-derived acetylcholin was described to stimulate the PCTR1 pathway in both murine and human ILC3s, favoring the resolution of inflammation (107).…”

Section: Local Regulation Of Human Helper Ilc3smentioning

confidence: 80%

Regulation of Human Innate Lymphoid Cells in the Context of Mucosal Inflammation

2020

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Since their identification as a unique cell population, innate lymphoid cells (ILCs) have revolutionized our understanding of immune responses, leaving their impact on multiple inflammatory and fibrotic pathologies without doubt. Thus, a tightly controlled regulation of local ILC numbers and their activity is of crucial importance. Even though this has been extensively studied in murine ILCs in the last few years, our knowledge of human ILCs is still lagging behind. Our review article will therefore summarize recent insights into the function of human ILCs and will particularly focus on their regulation under inflammatory conditions. The quality and intensity of ILC involvement into local immune responses at mucosal sites of the human body can potentially be modulated via three different axes: (1) activation of tissue-resident mature ILCs, (2) plasticity and local transdifferentiation of specific ILC subsets, and (3) tissue migration and accumulation of peripheral ILCs. Despite a still ongoing scientific effort in this field, already existing data on the fate of human ILCs under different pathologic conditions clearly indicate that all three of these mechanisms are of relevance for the clinical course of chronic inflammatory and autoimmune diseases and might likewise provide new target structures for future therapeutic strategies.

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Section: Local Regulation Of Human Helper Ilc3smentioning

confidence: 80%

Regulation of Human Innate Lymphoid Cells in the Context of Mucosal Inflammation

2020

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“…Of interest, several studies have shown a global stimulation of the Th17 response in asthma, with simultaneously increased expression of IL-17 and IL-22 in peripheral mononuclear blood cells (PMBC) and bronchial biopsies from asthmatic patients, this increase being even higher in severe asthmatic patients. Furthermore, increased levels of IL-17 and IL-22 were insensitive to steroids, a characteristic frequently found in patients with neutrophilic airway inflammation and with airway remodeling and specific to severe asthma (25,116,135,136). In a recent work, our group also reported airway remodeling and neutrophilia in a murine model of allergic asthma induced by dog allergen.…”

Section: Involvement Of Il-17 and Il-22 In Asthmamentioning

confidence: 99%

“…The involvement of IL-17 in asthma pathogenesis was further confirmed in murine models, which globally found that ovalbumin sensitization (inhaled, intraperitoneal, or epicutaneous route) followed by inhaled challenge was associated with Th17 response, up-regulation of IL-17 in airways, and that up-regulation of IL-17 enhanced airway neutrophilia and steroid-resistant AHR ( 112 – 115 ). IL-17 production is also increased in obesity-associated murine models of asthma and asthmatic pediatric patients ( 38 , 39 , 116 ). Data from murine models are summarized in Table 1 .…”

Section: Involvement Of Il-17 and Il-22 In Asthmamentioning

confidence: 99%

Role of Th17 Cytokines in Airway Remodeling in Asthma and Therapy Perspectives

et al. 2022

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Airway remodeling is a frequent pathological feature of severe asthma leading to permanent airway obstruction in up to 50% of cases and to respiratory disability. Although structural changes related to airway remodeling are well-characterized, immunological processes triggering and maintaining this phenomenon are still poorly understood. As a consequence, no biotherapy targeting cytokines are currently efficient to treat airway remodeling and only bronchial thermoplasty may have an effect on bronchial nerves and smooth muscles with uncertain clinical relevance. Th17 cytokines, including interleukin (IL)-17 and IL-22, play a role in neutrophilic inflammation in severe asthma and may be involved in airway remodeling. Indeed, IL-17 is increased in sputum from severe asthmatic patients, induces the expression of “profibrotic” cytokines by epithelial, endothelial cells and fibroblasts, and provokes human airway smooth muscle cell migration in in vitro studies. IL-22 is also increased in asthmatic samples, promotes myofibroblast differentiation, epithelial-mesenchymal transition and proliferation and migration of smooth muscle cells in vitro. Accordingly, we also found high levels of IL-17 and IL-22 in a mouse model of dog-allergen induced asthma characterized by a strong airway remodeling. Clinical trials found no effect of therapy targeting IL-17 in an unselected population of asthmatic patients but showed a potential benefit in a sub-population of patients exhibiting a high level of airway reversibility, suggesting a potential role on airway remodeling. Anti-IL-22 therapies have not been evaluated in asthma yet but were demonstrated efficient in severe atopic dermatitis including an effect on skin remodeling. In this review, we will address the role of Th17 cytokines in airway remodeling through data from in vitro, in vivo and translational studies, and examine the potential place of Th17-targeting therapies in the treatment of asthma with airway remodeling.

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“…In addition to Th17 lymphocytes, other cellular sources of IL-17 include invariant NK T cells, gd T cells, cytotoxic T cells, and especially group 3 innate lymphoid cells (ILC3) (71,72). High numbers of ILC3 were found in bronchoalveolar lavage fluid (BALF) from adults with severe asthma, as well as in blood of obese asthmatic children (72,73). Once secreted from Th17 lymphocytes, ILC3 and other cell types, IL-17A and IL-17F induce bronchial epithelial cells and sub-epithelial airway fibroblasts to release potent neutrophil chemoattractants including IL-8 (CXCL8) and CXCL1/GRO-a (74)(75)(76).…”

Section: Pathobiology Of Severe Asthmamentioning

confidence: 99%

Molecular Targets for Biological Therapies of Severe Asthma

et al. 2020

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Asthma is a heterogeneous respiratory disease characterized by usually reversible bronchial obstruction, which is clinically expressed by different phenotypes driven by complex pathobiological mechanisms (endotypes). Within this context, during the last years several molecular effectors and signalling pathways have emerged as suitable targets for biological therapies of severe asthma, refractory to standard treatments. Indeed, various therapeutic antibodies currently allow to intercept at different levels the chain of pathogenic events leading to type 2 (T2) airway inflammation. In addition to pro-allergic immunoglobulin E (IgE), that chronologically represents the first molecule against which an anti-asthma monoclonal antibody (omalizumab) was developed, today other targets are successfully exploited by biological treatments of severe asthma. In particular, pro-eosinophilic interleukin 5 (IL-5) can be targeted by mepolizumab or reslizumab, whereas benralizumab is a selective blocker of IL-5 receptor. Moreover, dupilumab behaves as a dual receptor antagonist of pleiotropic interleukins 4 (IL-4) and 13 (IL-13). Besides these drugs that are already available in medical practice, other biologics are under clinical development such as those targeting innate cytokines, also including the alarmin thymic stromal lymphopoietin (TSLP), which plays a key role in the pathogenesis of type 2 asthma. Therefore, ongoing and future biological therapies are significantly changing the global scenario of severe asthma management. These new therapeutic options make it possible to implement phenotype/endotype-specific treatments, that are delineating personalized approaches precisely addressing the individual traits of asthma pathobiology. Such tailored strategies are thus allowing to successfully target the immune-inflammatory responses underlying uncontrolled T2-high asthma.

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Obesity May Provide Pro-ILC3 Development Inflammatory Environment in Asthmatic Children

Cited by 20 publications

References 45 publications

Regulation of Human Innate Lymphoid Cells in the Context of Mucosal Inflammation

Regulation of Human Innate Lymphoid Cells in the Context of Mucosal Inflammation

Role of Th17 Cytokines in Airway Remodeling in Asthma and Therapy Perspectives

Molecular Targets for Biological Therapies of Severe Asthma

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