IL-10–producing innate lymphoid cells increased in patients with house dust mite allergic rhinitis following immunotherapy

Boonpiyathad, Tadech; Tantilipikorn, P.; Ruxrungtham, Kiat; Pradubpongsa, Panitan; Mitthamsiri, Wat; Piedvache, Aurélie; Thantiworasit, Pattarawat; Sirivichayakul, Sunee; Jacquet, Alain; Suratannon, Narissara; Chatchatee, Pantipa; Morisaki, Naho; Saito, Hirohisa; Sangasapaviriya, Atik; Matsumoto, Kenji; Morita, Hideaki

doi:10.1016/j.jaci.2020.10.029

Cited by 37 publications

(35 citation statements)

References 15 publications

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“…A study on murine airway allergy showed that in vivo generation of ILC2 10 s could effectively inhibit allergic airway inflammation by reducing the recruitment of eosinophils ( 17 ). Recently, an allergen-specific immunotherapy (AIT) cohort control study for patients with house dust mite allergic rhinitis found that the percentages of IL-10 + CTLA-4 + ILCs in the responders after 2 years of AIT were increased by 3.2% (95% CI = 0.7%-5.7%) and were higher than in the nonresponders (–0.9% [95% CI = –4.5% to 2.7%])) and placebo-treated patients (1.2% [95% CI = –2.4% to 4.8%]), IL-10–producing innate lymphoid cells increased in patients with house dust mite allergic rhinitis following immunotherapy ( 94 ). In addition, in a prospective, double-blind, placebo-controlled trial, Golebski et al reported that, compared with healthy subjects, patients with grass-pollen allergy had lower frequency of IL-10 + KLRG1 + ILC2s, and patients who received grass-pollen sublingual immunotherapy restored the ability of ILC2 to produce IL-10 ( 95 ).…”

Section: Il-10-producing Ilcs In Diseasesmentioning

confidence: 94%

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: Il-10-producing Ilcs In Diseasesmentioning

confidence: 94%

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

Sun

Wu²,

Zhang³

et al. 2021

Front. Immunol.

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“…Indeed, based on the induction of “regulatory” IL-10-secreting ILC2s upon AIT in allergic patients, one can hypothesize that differences in functional polarization (eg IL-10 versus IL-13 secretion) might still be captured when cytokines are used during the in vitro cell propagation. 58 Moreover, it would be informative to test whether a resting period in IL-2 and IL-7 only after expansion in the presence of IL-25 and IL-33 would restore their capacity to respond to a further in vitro stimulation.…”

Section: Discussionmentioning

confidence: 99%

Healthy and Patient Type 2 Innate Lymphoid Cells are Differently Affected by in vitro Culture Conditions

Falquet¹,

Ercolano²,

Jandus³

et al. 2021

JAA

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Background Type 2 innate lymphoid cells (ILC2s) have emerged as key players in the development of type 2 driven diseases such as allergy and asthma. Due to their low number in the circulation, in vitro expansion is needed to unravel their mechanisms of action. Purpose The aim of this study is to assess the impact of different culture conditions and address whether the method of expansion may distinctly affect healthy donor or patient-derived ILC2s. Methods Here, we described the impact of six different culture conditions on the proliferation, phenotype and function of human ILC2s freshly obtained from healthy donors (healthy ILC2s) and allergic patients (patient ILC2s). Results We showed that the cytokine cocktail or the PHA induced the highest proliferation of healthy ILC2s and patient ILC2s, respectively. We observed that the stromal cells OP9, used as ILC2 feeders, did not boost their proliferation, but impaired the activation marker expression and the function of patient ILC2s. Furthermore, we demonstrated that the culture conditions differently impacted the activation state of c-Kit high and c-Kit low ILC2s, in both healthy donors and allergic patients. Last, we also observed that ILC2s expanded only with IL-2 and IL-7 were the most prone to secrete IL-5 and IL-13 upon IL-33 stimulation. In contrast, in patients, the addition of OP9 cells during the expansion restrained their type 2 cytokine secretory functions. Conclusion This report highlights that culture conditions distinctly impacted on the healthy or patient ILC2 behavior, with important consequences for their study in disease settings.

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“…These regulatory ILC2s are not equivalent to Treg cells as they lack the Treg master transcription factor FoxP3., 140,141 Moreover, these IL‐10‐producing ILCs are functional and can suppress Th2 cell responses (Figure 5). 142 These regulatory ILC2s are induced following subcutaneous (SCIT) and sublingual grass pollen immunotherapy (SLIT), 141 as well as house dust mite SCIT treatment 143 . These observations suggest a potential utility of regulatory ILCs as a target for the treatment of food allergy.…”

Section: Therapeutic Applications and Future Perspectivesmentioning

confidence: 99%

Innate lymphoid cells: The missing part of a puzzle in food allergy

Şahiner

Layhadi

Golebski

et al. 2021

Allergy

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Food allergy is an increasingly prevalent disease driven by uncontrolled type 2 immune response. Currently, knowledge about the underlying mechanisms that initiate and promote the immune response to dietary allergens is limited. Patients with food allergy are commonly sensitized through the skin in their early life, later on developing allergy symptoms within the gastrointestinal tract. Food allergy results from a dysregulated type 2 response to food allergens, characterized by enhanced levels of IgE, IL‐4, IL‐5, and IL‐13 with infiltration of mast cells, eosinophils, and basophils. Recent studies raised a possible role for the involvement of innate lymphoid cells (ILCs) in driving food allergy. Unlike lymphocytes, ILCs lack They represent a group of lymphocytes that lack specific antigen receptors. ILCs contribute to immune responses not only by releasing cytokines and other mediators but also by responding to cytokines produced by activated cells in their local microenvironment. Due to their localization at barrier surfaces of the airways, gut, and skin, ILCs form a link between the innate and adaptive immunity. This review summarizes recent evidence on how skin and gastrointestinal mucosal immune system contribute to both homeostasis and the development of food allergy, as well as the involvement of ILCs toward inflammatory processes and regulatory mechanisms.

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IL-10–producing innate lymphoid cells increased in patients with house dust mite allergic rhinitis following immunotherapy

Cited by 37 publications

References 15 publications

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

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

Healthy and Patient Type 2 Innate Lymphoid Cells are Differently Affected by in vitro Culture Conditions

Innate lymphoid cells: The missing part of a puzzle in food allergy

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