New insights into the function, development, and plasticity of type 2 innate lymphoid cells

Krabbendam, Lisette; Bal, Suzanne M.; Spits, Hergen; Golebski, Korneliusz

doi:10.1111/imr.12708

Cited by 70 publications

(65 citation statements)

References 96 publications

(140 reference statements)

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“…Functional plasticity, or the capacity to adopt phenotypes similar to other ILC subsets, provides the potential to fine-tune immune responses to different types of cytokines and enables the rapid adaption when confronted with pathogens (see also ref. 50 ). Several studies have demonstrated this interconversion at least in vitro.…”

Section: Introductionmentioning

confidence: 99%

Pulmonary group 2 innate lymphoid cells: surprises and challenges

et al. 2019

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Group 2 innate lymphoid cells (ILC2s) are a recently described subset of innate lymphocytes with important immune and homeostatic functions at multiple tissue sites, especially the lung. These cells expand locally after birth and during postnatal lung maturation and are present in the lung and other peripheral organs. They are modified by a variety of processes and mediate inflammatory responses to respiratory pathogens, inhaled allergens and noxious particles. Here, we review the emerging roles of ILC2s in pulmonary homeostasis and discuss recent and surprising advances in our understanding of how hormones, age, neurotransmitters, environmental challenges, and infection influence ILC2s. We also review how these responses may underpin the development, progression and severity of pulmonary inflammation and chronic lung diseases and highlight some of the remaining challenges for ILC2 biology.Mucosal Immunology (2019) 12:299-311; https://doi.

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Section: Introductionmentioning

confidence: 99%

Pulmonary group 2 innate lymphoid cells: surprises and challenges

et al. 2019

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“…Further, several studies have demonstrated signi cant heterogeneity and plasticity of ILCs (reviewed in 61 ). For example, in addition to conventional ILC3s, IL-17 production occurs from other ILC sources including "in ammatory" iILC2s (or ILC2-17 s) induced by IL-25, cysteinyl leukotrienes, and notch signaling 9,10,62 .…”

Section: Discussionmentioning

confidence: 99%

RNA-binding protein RBM3 negatively regulates innate lymphoid cells (ILCs) and lung inflammation

Badrani¹,

Amadeo²,

Cavagnero³

et al. 2020

Preprint

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Innate lymphoid cells (ILCs) promote lung inflammation through cytokine production in diseases such as asthma. RNA-binding proteins (RBPs) are critical post-transcriptional regulators of cellular function, including inflammatory responses, though the role of RBPs in innate lymphoid cells is unknown. Here, we demonstrate that RNA-binding motif 3 (RBM3) is one of the most highly expressed RBPs in Thy1.2 + lung ILCs after fungal allergen challenge and is further induced by epithelial cytokines TSLP and IL-33 in both human and mouse ILCs. Single (rbm3-/-) and double (rbm3-/-rag2-/-) knockout mice exposed via the airway to the asthma-associated fungal allergen Alternaria alternata displayed increases in eosinophilic lung inflammation and ILC activation compared to control mice. In addition to increased Th2 cytokine production, rbm3-/- ILCs produced elevated IL-17A. The negative regulation by RBM3 in ILC responses was direct as purified rbm3-/- ILCs were hyperinflammatory in vitro and in vivo after stimulation with IL-33. Transcriptomic analysis by RNA-sequencing of rbm3-/- lung ILCs showed increased type 2 and 17 cytokines as well as global expression differences in critical cytokines, receptors, transcription factors, and survival transcripts compared with WT ILCs. Intriguingly, these transcript changes did not correlate with the presence of AU-rich elements (AREs), which RBM3 is known to bind. Thus, regulation of ILC responses by RNA-binding proteins offers novel mechanistic insight into lung ILC biology and ILC-driven inflammatory diseases.

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“…ILCs are subdivided into three groups: ILC1, ILC2, and ILC3, based on their cytokine profiles and expression of specific transcription factors, mirroring the classification of CD4 + T helper cell subsets into TH1, TH2, and TH17 cells. Type 2 ILCs (ILC2s) resemble TH2 cells as they require the transcription factor GATA‐3; produce type 2 cytokines IL‐4, IL‐5, IL‐9, and IL‐13; and play important roles in immunity against pathogens and type 2 inflammation (Krabbendam et al , 2018). ILC2s also promote tissue recovery following acute injury in multiple organs, such as lung, intestine, and kidney (Monticelli et al , 2011; Cao et al , 2018).…”

Section: Introductionmentioning

confidence: 99%

IL ‐10 producing type 2 innate lymphoid cells prolong islet allograft survival

Huang

Wang

et al. 2020

EMBO Mol Med

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Type 2 innate lymphoid cells (ILC2s) are a subset of ILCs with critical roles in immunoregulation. However, the possible role of ILC2s as immunotherapy against allograft rejection remains unclear. Here, we show that IL‐33 significantly prolonged islet allograft survival. IL‐33‐treated mice had elevated numbers of ILC2s and regulatory T cells (Tregs). Depletion of Tregs partially abolished the protective effect of IL‐33 on allograft survival, and additional ILC2 depletion in Treg‐depleted DEREG mice completely abolished the protective effects of IL‐33, indicating that ILC2s play critical roles in IL‐33‐mediated islet graft protection. Two subsets of ILC2s were identified in islet allografts of IL‐33‐treated mice: IL‐10 producing ILC2s (ILC210) and non‐IL‐10 producing ILC2s (non‐ILC10). Intravenous transfer of ILC210 cells, but not non‐ILC10, prolonged islet allograft survival in an IL‐10‐dependent manner. Locally transferred ILC210 cells led to long‐term islet graft survival, suggesting that ILC210 cells are required within the allograft for maximal suppressive effect and graft protection. This study has uncovered a major protective role of ILC210 in islet transplantation which could be potentiated as a therapeutic strategy.

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New insights into the function, development, and plasticity of type 2 innate lymphoid cells

Cited by 70 publications

References 96 publications

Pulmonary group 2 innate lymphoid cells: surprises and challenges

Pulmonary group 2 innate lymphoid cells: surprises and challenges

RNA-binding protein RBM3 negatively regulates innate lymphoid cells (ILCs) and lung inflammation

IL ‐10 producing type 2 innate lymphoid cells prolong islet allograft survival

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