Innate Lymphoid Cells: A Promising New Regulator in Fibrotic Diseases

Zhang, Yi; Tang, Jun; Tian, Zhiqiang; Velkinburgh, Jennifer C. van; Song, Jianxun; Wu, Yuzhang; Ni, Bing

doi:10.3109/08830185.2015.1068304

Cited by 15 publications

(12 citation statements)

References 131 publications

(181 reference statements)

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“…Because ILC2s have recently been associated with fibrotic diseases where type 2 cytokines are considered the most potent profibrotic factors through direct activation of fibroblasts [42,43], it is conceivable that ILC2s also contribute to airway remodeling in asthma. In agreement with this, chronic exposure of mice to a cocktail of Alternaria, Aspergillus, and HDM was shown to induce robust airway inflammation, hyperresponsiveness, and remodeling by a mechanism dependent on adaptive immunity [44].…”

Section: Discussionmentioning

confidence: 99%

T cells are necessary for ILC2 activation in house dust mite‐induced allergic airway inflammation in mice

Bruijn

Tindemans

et al. 2016

Eur J Immunol

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Allergic asthma is a chronic inflammation of the airways mediated by an adaptive type 2 immune response. Upon allergen exposure, group 2 innate lymphoid cells (ILC2s) can be rapidly activated and represent an early innate source of IL-5 and IL-13. Here, we used a house dust mite (HDM)-driven asthma mouse model to study the induction of ILC2s in allergic airway inflammation. In BALF, lungs, and lymph nodes, ILC2 activation is critically dependent on prior sensitization with HDM. Importantly, T cells are required for ILC2 induction, whereby T-cell activation precedes ILC2 induction. During HDM-driven allergic airway inflammation the accumulation of ILC2s in BALF is IL-33 independent, although infiltrating ILC2s produce less cytokines in Il33 −/− mice. Transfer of in vitro polarized OVA-specific OT-II Th2 cells alone or in combination with Th17 cells followed by OVA and HDM challenge is not sufficient to induce ILC2, despite significant eosinophilic inflammation and T-cell activation. In this asthma model, ILC2s are therefore not an early source of Th2 cytokines, but rather contribute to type 2 inflammation in which Th2 cells play a key role. Taken together, ILC2 induction in HDM-mediated allergic airway inflammation in mice critically depends on activation of T cells.Keywords: Allergy · Asthma · Group 2 innate lymphoid cells (ILC2s) · House dust mite · Th2 cellsAdditional supporting information may be found in the online version of this article at the publisher's web-site IntroductionAsthma is a heterogeneous disease involving chronic inflammation of the airways and is characterized by episodes of coughing, wheezing, and shortness of breath. Multiple genetic predispositions and environmental factors contribute to asthma development and it is estimated that ß300 million people are affected worldwide. The asthma syndrome is divided into distinct disease entities with specific mechanisms, which have been called asthma endotypes [1,2]. The most prevalent endotype is allergic asthma, showing a strong association between exacerbations and repeated Correspondence: Dr. Rudi W. Hendriks e-mail: r.hendriks@erasmusmc.nl exposure to allergens such as pollen, fungi, or house dust mite (HDM). Allergic asthma is thought to be a classic Th2-mediated disease in which the signature effector cytokines IL-4, IL-5, and IL-13 are key orchestrators of persistent inflammation, airway hyperresponsiveness and remodeling, smooth muscle cell hyperplasia, mucous cell metaplasia, and increased angiogenesis (reviewed in [2,3]).Although production of IL-5 and IL-13 by a non-T/non-B lymphocyte population in response to IL-25 was first reported by Fort et al. [4], only recently these cells were accurately characterized and defined as a novel cell population that is negative for classic hematopoietic lineage markers and expresses Sca-1, CD117 (c-kit), CD25 (IL-2Rα), CD127 (IL-7Rα), and T1/ST2 (IL-33R) [5][6][7]. These innate cells are currently referred to as group 2 innate lymphoid cells (ILC2s) and were found to produce IL-13, which is [24]. Ho...

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Section: Discussionmentioning

confidence: 99%

T cells are necessary for ILC2 activation in house dust mite‐induced allergic airway inflammation in mice

Bruijn

Tindemans

et al. 2016

Eur J Immunol

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“…While TGFβ has been established as an essential mediator of fibrosis, IL-13 is also recognized to play a role both in a TGFβ-dependent manner, as shown in the context of colitis but also through an independent mechanism, as demonstrated in liver fibrosis [72][73][74]. Due to their direct interaction with stromal cells (e.g., sensing IL-33 in adipose tissue) and their production of IL-13 both at steady state and during inflammation, ILC2s are, potentially, key mediators of fibrosis development and are implicated in several fibrotic conditions [75].…”

Section: Ilc2s In Tissue Fibrosismentioning

confidence: 99%

Group 2 Innate Lymphoid Cells: Central Players in a Recurring Theme of Repair and Regeneration

Messing

Jan-Abu

McNagny

2020

IJMS

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Innate lymphoid cells (ILCs) are recently discovered innate counterparts to the well-established T helper cell subsets and are most abundant at barrier surfaces, where they participate in tissue homeostasis and inflammatory responses against invading pathogens. Group 2 innate lymphoid cells (ILC2s) share cytokine and transcription factor expression profiles with type-2 helper T cells and are primarily associated with immune responses against allergens and helminth infections. Emerging data, however, suggests that ILC2s are also key regulators in other inflammatory settings; both in a beneficial context, such as the establishment of neonatal immunity, tissue repair, and homeostasis, and in the context of pathological tissue damage and disease, such as fibrosis development. This review focuses on the interactions of ILC2s with stromal cells, eosinophils, macrophages, and T regulatory cells that are common to the different settings in which type-2 immunity has been explored. We further discuss how an understanding of these interactions can reveal new avenues of therapeutic tissue regeneration, where the role of ILC2s is yet to be fully established.

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“…Pulmonary fibrosis occurs as a result of damage and scarring of the lung parenchyma that can have numerous causes including, environmental toxins, medication side effects, radiation therapy, and autoimmune conditions. In fibrotic disease, chronic inflammation and persistent extracellular matrix deposition can lead to remodeling and progressive tissue destruction (87). This remodeling and extracellular matrix deposition is largely driven by connective tissue cells, such as fibroblasts, whose functions are directly affected by pro-fibrotic cytokines produced by adaptive and innate immune cells (88).…”

Section: Autoimmune Diseasementioning

confidence: 99%

Type 3 ILCs in Lung Disease

et al. 2019

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The lungs represent a complex immune setting, balancing external environmental signals with a poised immune response that must protect from infection, mediate tissue repair, and maintain lung function. Innate lymphoid cells (ILCs) play a central role in tissue repair and homeostasis, and mediate protective immunity in a variety of mucosal tissues, including the lung. All three ILC subsets are present in the airways of both mice and humans; and ILC2s shown to have pivotal roles in asthma, airway hyper-responsiveness, and parasitic worm infection. The involvement of ILC3s in respiratory diseases is less well-defined, but they are known to be critical in homeostasis, infection and inflammation at other mucosal barriers, such as the gut. Moreover, they are important players in the IL17/IL22 axis, which is key to lung health. In this review, we discuss the emerging role of ILC3s in the context of infectious and inflammatory lung diseases, with a focus on data from human subjects.

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Innate Lymphoid Cells: A Promising New Regulator in Fibrotic Diseases

Cited by 15 publications

References 131 publications

T cells are necessary for ILC2 activation in house dust mite‐induced allergic airway inflammation in mice

T cells are necessary for ILC2 activation in house dust mite‐induced allergic airway inflammation in mice

Group 2 Innate Lymphoid Cells: Central Players in a Recurring Theme of Repair and Regeneration

Type 3 ILCs in Lung Disease

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