IL-10 production by ILC2s requires Blimp-1 and cMaf, modulates cellular metabolism, and ameliorates airway hyperreactivity

Howard, Emily; Lewis, Gavin; Galle-Treger, Lauriane; Hurrell, Benjamin P.; Helou, Doumet Georges; Shafiei-Jahani, Pedram; Painter, Jacob D.; Muench, German Aleman; Soroosh, Pejman; Akbari, Omid

doi:10.1016/j.jaci.2020.08.024

Cited by 44 publications

(53 citation statements)

References 53 publications

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“…However, in addition to LTi cells, helper-like ILCs have also been reported to have the ability to produce IL-10 under certain conditions, suggesting that IL-10 production is not a unique feature of NK cells. Seehus et al fist reported that administration of IL-33 induced IL-10 production in mouse lung ILC2s, and they termed this population ILC2 10 s ( 17 ), and subsequent studies further indicate that severe and recurrent allergic pulmonary inflammation or asthma are the necessary conditions for the presence of ILC2 10 s ( 18 ). However, unlike these pulmonary IL-10-producing ILC2s, which require activation and specific stimulation to produce IL-10, Wang et al reported that there is a unique subset of IL-10 constitutively expressed in the intestine ( 19 ).…”

Section: Introductionmentioning

confidence: 99%

IL-10-Producing ILCs: Molecular Mechanisms and Disease Relevance

Sun

Wu²,

Zhang³

et al. 2021

Front. Immunol.

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Innate lymphoid cells (ILCs) are mainly composed of natural killer (NK) cells and helper-like lymphoid cells, which play a vital role in maintaining tissue homeostasis, enhancing adaptive immunity and regulating tissue inflammation. Alteration of the distribution and function of ILCs subgroups are closely related to the pathogenesis of inflammatory diseases and cancers. Interleukin-10 (IL-10) is a highly pleiotropic cytokine, and can be secreted by several cell types, among of which ILCs are recently verified to be a key source of IL-10. So far, the stable production of IL-10 can only be observed in certain NK subsets and ILC2s. Though the regulatory mechanisms for ILCs to produce IL-10 are pivotal for understanding ILCs and potential intervenes of diseases, which however is largely unknown yet. The published studies show that ILCs do not share exactly the same mechanisms for IL-10 production with helper T cells. In this review, the molecular mechanisms regulating IL-10 production in NK cells and ILC2s are discussed in details for the first time, and the role of IL-10-producing ILCs in diseases such as infections, allergies, and cancers are summarized.

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Section: Introductionmentioning

confidence: 99%

IL-10-Producing ILCs: Molecular Mechanisms and Disease Relevance

Sun

Wu²,

Zhang³

et al. 2021

Front. Immunol.

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“…In IBD patients an increased ILC2 frequency was observed at inflamed intestinal sites (34), suggesting a certain clinical relevance. Just recently, a regulatory subset of IL-10 producing ILC2s was described to have a protective effect in the context of grass-pollen allergy and lung inflammation (75,76). This was not only mediated by their ability to dampen disease-driving type-2 immune responses (75,76), but additionally relied on the restoration of the epithelial barrier (75).…”

Section: Ilc-iec Interactionsmentioning

confidence: 99%

“…Just recently, a regulatory subset of IL-10 producing ILC2s was described to have a protective effect in the context of grass-pollen allergy and lung inflammation (75,76). This was not only mediated by their ability to dampen disease-driving type-2 immune responses (75,76), but additionally relied on the restoration of the epithelial barrier (75). Whether this regulatory ILC subset is relevant in the inflamed gut as well, has to be determined in future studies, though.…”

Section: Ilc-iec Interactionsmentioning

confidence: 99%

Innate Lymphoid Cells as Regulators of Epithelial Integrity: Therapeutic Implications for Inflammatory Bowel Diseases

2021

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The occurrence of epithelial defects in the gut relevantly contributes to the pathogenesis of inflammatory bowel diseases (IBD), whereby the impairment of intestinal epithelial barrier integrity seems to represent a primary trigger as well as a disease amplifying consequence of the chronic inflammatory process. Besides epithelial cell intrinsic factors, accumulated and overwhelmingly activated immune cells and their secretome have been identified as critical modulators of the pathologically altered intestinal epithelial cell (IEC) function in IBD. In this context, over the last 10 years increasing levels of attention have been paid to the group of innate lymphoid cells (ILCs). This is in particular due to a preferential location of these rather newly described innate immune cells in close proximity to mucosal barriers, their profound capacity to secrete effector cytokines and their numerical and functional alteration under chronic inflammatory conditions. Aiming on a comprehensive and updated summary of our current understanding of the bidirectional mucosal crosstalk between ILCs and IECs, this review article will in particular focus on the potential capacity of gut infiltrating type-1, type-2, and type-3 helper ILCs (ILC1s, ILC2s, and ILC3s, respectively) to impact on the survival, differentiation, and barrier function of IECs. Based on data acquired in IBD patients or in experimental models of colitis, we will discuss whether the different ILC subgroups could serve as potential therapeutic targets for maintenance of epithelial integrity and/or mucosal healing in IBD.

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“…IL-10 exerts suppressive effects on DC, macrophages and Th2 cells, and stimulates the expansion of Tregs [70]. Interestingly, these cells shift from the fatty acid oxidation pathway conventionally used for proinflammatory effector functions, to the glycolytic pathway for IL-10 production [71]. Few IL-10+ ILC2s have been detected in the intestine [47] where their expression was induced in vitro by IL-2, IL-4, IL-27, IL-10 and NMU.…”

Section: Enhancing and Regulatory Function Of Ilc2smentioning

confidence: 99%

“…As described, IL-4 production can regulate IL-10 synthesis by ILC2s through the upregulation of cMaf and Blimp-1 transcription factors. IL-10+ILC2s utilize both autocrine and paracrine signaling to suppress proinflammatory ILC2s effector functions, shifting from the fatty acid oxidation pathway usually utilized for proinflammatory activity [70,71]. The overexpression of IL-4Rα in tumor cells is usually associated with poor prognosis in some human cancer (bladder, head-neck carcinomas, etc.)…”

Section: Ilc2s As Therapeutic Targets In Tumorsmentioning

confidence: 99%

Group 2 Innate Lymphoid Cells: A Double-Edged Sword in Cancer?

Maggi

Veneziani

Moretta

et al. 2020

Cancers

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Group 2 Innate Lymphoid Cells (ILC2s) belong to the family of helper ILCs which provide host defense against infectious agents, participate in inflammatory responses and mediate lymphoid organogenesis and tissue repair, mainly at the skin and mucosal level. Based on their transcriptional, phenotypic and functional profile, ILC2s mirror the features of the adaptive CD4+ Th2 cell subset, both contributing to the so-called type 2 immune response. Similar to other ILCs, ILC2s are rapidly activated by signals deriving from tissue and/or other tissue-resident immune cells. The biologic activity of ILCs needs to be tightly regulated in order to prevent them from contributing to severe inflammation and damage in several organs. Indeed, ILC2s display both enhancing and regulatory roles in several pathophysiological conditions, including tumors. In this review, we summarize the actual knowledge about ILC2s ability to induce or impair a protective immune response, their pro- or antitumor activity in murine models, human (children and adults) pathologies and the potential strategies to improve cancer immunotherapy by exploiting the features of ILC2s.

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IL-10 production by ILC2s requires Blimp-1 and cMaf, modulates cellular metabolism, and ameliorates airway hyperreactivity

Cited by 44 publications

References 53 publications

IL-10-Producing ILCs: Molecular Mechanisms and Disease Relevance

IL-10-Producing ILCs: Molecular Mechanisms and Disease Relevance

Innate Lymphoid Cells as Regulators of Epithelial Integrity: Therapeutic Implications for Inflammatory Bowel Diseases

Group 2 Innate Lymphoid Cells: A Double-Edged Sword in Cancer?

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