Thymic stromal lymphopoietin induces corticosteroid resistance in natural helper cells during airway inflammation

Kabata, Hiroki; Moro, Kazuyo; Fukunaga, Koichi; Suzuki, Yuzo; Miyata, Jun; Masaki, Katsunori; Betsuyaku, Tomoko; Koyasu, Shigeo; Asano, Koichiro

doi:10.1038/ncomms3675

Cited by 279 publications

(250 citation statements)

References 42 publications

Supporting

Mentioning

229

Contrasting

Unclassified

Order By: Relevance

“…ILC2 numbers are increased in sputum and peripheral blood of patients with severe asthma compared to mild asthmatics or healthy controls [45,46]. Importantly, evidence was found for a role of uncontrolled localized production of IL-5 and IL-13 by a steroid-insensitive population of ILC2s, in agreement with in vitro studies showing that ILC2s are steroidinsensitive in the presence of TSLP [46,47].In conclusion, the contribution of ILC2s to asthma is related to the properties of the allergen. In papain-induced inflammation, ILC2s are rapidly induced prior to T-cell activation and ILC2-derived IL-13 is essential for the initiation of T-cell activation and Th2 differentiation [13].…”

supporting

confidence: 73%

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

View full text Add to dashboard Cite

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...

show abstract

supporting

confidence: 73%

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

View full text Add to dashboard Cite

show abstract

“…Levels of IL-33 correlated with increased reticular basement membrane thickness in endobronchial biopsies, and mouse studies in which neonatal mice were dosed with house dust mite allergens indicated that, in contrast to IL-13 levels, IL-33 concentrations were steroid resistant. A similar link between IL-33 stimulation in the context of ovalbumin (OVA) challenge in the lung and steroid resistance was recently reported to be due to TSLP (61). When mice were dosed with only IL-33, the inflammatory response could be inhibited by treatment with dexamethasone.…”

Section: Ilc2 In Lung Allergy and Inflammationmentioning

confidence: 79%

Type-2 Innate Lymphoid Cells in Asthma and Allergy

McKenzie

2014

Annals ATS

112

View full text Add to dashboard Cite

Type-2 innate lymphoid cells (ILC2) belong to an expanding family of innate lymphocytes that provide a potent source of immune effector cytokines at the initiation of immune responses. ILC2 arise, under the control of the transcription factors RORa and GATA3, from lymphoid progenitors in the bone marrow, to secrete type-2 cytokines including IL-5 and IL-13. Using experimental models, ILC2 have been implicated in allergic diseases, such as asthma and atopic dermatitis, but also in metabolic homeostasis. Furthermore, recent reports have indicated that ILC2 not only play roles at the initiation of type-2 immunity but can also contribute to chronic pathology, such as fibrosis, and can impact on the priming of the adaptive T-cell response. The identification of ILC2 in patients with allergic dermatitis and allergic rhinitis indicates that these cells may represent new therapeutic targets.Keywords: type-2 immunity; type-2 innate lymphoid cells; innate immunity; cytokines However, a recent major paradigm shift has added another layer of complexity to immunoregulation by cytokines with the discovery of innate lymphoid cells (ILCs) (2). ILCs produce many Th cell-associated cytokines but do not express cell surface markers associated with other immune cell lineages (lineage-negative [Lin 2 ]) and do not express a T-cell receptor. The ILC family now includes ILC1 (predominantly IFN-g-expressing cells), ILC2 (predominantly IL-5-and IL-13-expressing cells), and ILC3 (predominantly IL-22-and IL-17-expressing cells) (3-6). Due to their recent discovery, our knowledge of these cells is still rather rudimentary, but major roles are emerging for ILCs in protective immunity against parasitic helminths (ILC2) (7-9) and bacteria (ILC1 and ILC3) (10-12), and in autoimmune disorders (ILC1 and ILC3) (13), allergic disease (ILC2) (14-16), and obesity (17)(18)(19).Recent comprehensive reviews have described the identification and phenotypic characterization of 20). This review focuses on the most recent advances in our understanding of the factors that regulate ILC2 development and how these cells contribute to allergy and lung inflammation. ILC2ILC2 are found in the blood, spleen, intestine, liver, lung, fat-associated lymphoid clusters, and lymph nodes of mice (7-9). They are Lin 2 (CD3CD4CD8CD19CD11bCD11cFceR1 NK1.1Gr1 2 ) CD45 1 CD127

show abstract

“…Subsequently, the predominantly epithelial cell-derived cytokine thymic stromal lymphopoietin (TSLP) has also been shown to be a key regulator of ILC2 function (Halim et al 2012a;Kim et al 2013a). Recent studies have shown that TSLP induces GATA3 expression in human ILC2s (Mjosberg et al 2012) and promotes corticosteroid resistance to IL-33-mediated activation of ILC2s in the lung (Kabata et al 2013). In addition, enforced expression of GATA3 in T cells and ILC2s results in elevated expression of IL-5 and IL-13 and enhanced susceptibility to allergic airway disease in mice (Kleinjan et al 2014).…”

Section: Regulation and Effector Functions Of Ilc2smentioning

confidence: 99%

“…A recent study has shown that TSLP can contribute to ILC2 activation that promotes corticosteroid resistance in the context of IL-33-mediated airway inflammation (Kabata et al 2013). Further, recent reports suggest that other factors, such as eicosanoids, could also play a key role in promoting ILC2 responses in the inflamed lung (Barnig et al 2013;Doherty et al 2013).…”

Section: Ilc2s and Allergic Airway Inflammationmentioning

confidence: 99%

Group 2 Innate Lymphoid Cells in Health and Disease

Kim

Artis

2015

Cold Spring Harb Perspect Biol

View full text Add to dashboard Cite

Group 2 innate lymphoid cells (ILC2s) play critical roles in anti-helminth immunity, airway epithelial repair, and metabolic homeostasis. Recently, these cells have also emerged as key players in the development of allergic inflammation at multiple barrier surfaces. ILC2s arise from common lymphoid progenitors in the bone marrow, are dependent on the transcription factors RORa, GATA3, and TCF-1, and produce the type 2 cytokines interleukin (IL)-4, IL-5, IL-9, and/or IL-13. The epithelial cell -derived cytokines IL-25, IL-33, and TSLP regulate the activation and effector functions of ILC2s, and recent studies suggest that their responsiveness to these cytokines and other factors may depend on their tissue environment. In this review, we focus on recent advances in our understanding of the various factors that regulate ILC2 function in the context of immunity, inflammation, and tissue repair across multiple organ systems.

show abstract

Thymic stromal lymphopoietin induces corticosteroid resistance in natural helper cells during airway inflammation

Cited by 279 publications

References 42 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

Type-2 Innate Lymphoid Cells in Asthma and Allergy

Group 2 Innate Lymphoid Cells in Health and Disease

Contact Info

Product

Resources

About