IL-27 suppresses type 2 immune responses in vivo via direct effects on group 2 innate lymphoid cells

Mchedlidze, Tamar; Kindermann, Markus; Neves, A.; Voehringer, David; Neurath, Markus F.; Wirtz, Stefan

doi:10.1038/mi.2016.20

Cited by 61 publications

(60 citation statements)

References 55 publications

(78 reference statements)

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“…Many different groups have confirmed that type 1 IFNs, type 2 IFN, and IL‐27 suppress the proliferation and type 2 cytokine production from mouse and human ILC2s . Specifically, IFN‐β and IFN‐γ strongly suppress the activation of mouse ILC2s in response to IL‐33 or IL‐2 + IL‐25 stimulation .…”

Section: Suppressive Cytokines (Type 1 Ifns Type 2 Ifn (Ifn‐γ) Il‐2mentioning

confidence: 97%

The group 2 innate lymphoid cell (ILC2) regulatory network and its underlying mechanisms

Kabata

Moro

Koyasu

2018

Immunological Reviews

207

182

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Summary Group 2 innate lymphoid cells (ILC2s) play critical roles in the induction of type 2 inflammation, response to parasite infection, metabolic homeostasis, and tissue repair. These multifunctional roles of ILC2s are tightly controlled by complex regulatory systems in the local microenvironment, the disruption of which may cause various health problems. This review summarizes up‐to‐date knowledge regarding positive and negative regulators for ILC2s based on their function and signaling pathways, including activating cytokines (IL‐33, IL‐25; MAPK, NF‐κB pathways), co‐stimulatory cytokines (IL‐2, IL‐7, IL‐9, TSLP; STAT5, IL‐4; STAT6, TNF superfamily; MAPK, NF‐κB pathways), suppressive cytokines (type1 IFNs, IFN‐γ, IL‐27; STAT1, IL‐10, TGF‐β), transdifferentiation cytokines (IL‐12; STAT4, IL‐1β, IL‐18), lipid mediators (LTC4, LTD4, LTE4, PGD2; Ca2+‐NFAT pathways, PGE2, PGI2; AC/cAMP/PKA pathways, LXA4, LTB4), neuropeptides (NMU; Ca2+‐NFAT, MAPK pathways, VIP, CGRP, catecholamine, acetylcholine), sex hormones (androgen, estrogen), nutrients (butyrate; HDAC inhibitors, vitamins), and cell‐to‐cell interactions (ICOSL‐ICOS; STAT5, B7‐H6‐NKp30, E‐cadherin‐KLRG1). This comprehensive review affords a better understanding of the regulatory network system for ILC2s, providing impetus to develop new treatment strategies for ILC2‐related health problems.

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Section: Suppressive Cytokines (Type 1 Ifns Type 2 Ifn (Ifn‐γ) Il‐2mentioning

confidence: 97%

The group 2 innate lymphoid cell (ILC2) regulatory network and its underlying mechanisms

Kabata

Moro

Koyasu

2018

Immunological Reviews

207

182

View full text Add to dashboard Cite

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“…The many functions of ILC2s in the context of models of allergic disease suggest that ILC2 populations might represent a fruitful therapeutic target. It is also possible that negative regulators of ILC2 responses such as type 1(79) and type 2 interferons(80), IL-27(81, 82), KLRG1 signaling by E-cadherin(66), lipoxin A4(83), and T regulatory cells(84, 85) could also be manipulated to reduce ILC2 activation in the context of allergic inflammation.…”

Section: Innate Immunitymentioning

confidence: 99%

Type 2 Cytokine Responses: Regulating Immunity to Helminth Parasites and Allergic Inflammation

2017

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Purpose of Review It is well established that T helper type 2 (TH2) immune responses are necessary to provide protection against helminth parasites but also to promote the detrimental inflammation associated with allergies and asthma. Given the importance of type 2 immunity and inflammation, many studies have focused on better understanding the factors that regulate TH2 cell development and activation. As a result, significant progress has been made in understanding the signaling pathways and molecular events necessary to promote TH2 cell polarization. In addition to the adaptive compartment, emerging studies are better defining the innate immune pathways needed to promote TH2 cell responses. Given the recent and substantial growth of this field, the purpose of this review is to highlight recent studies defining the innate immune events that promote immunity to helminth parasites and allergic inflammation. Recent Findings Emerging studies have begun to elucidate the importance of cytokine alarmins such as thymic stromal lymphopoietin (TSLP), IL-25 (IL-17E) and IL-33 in promoting type 2 immunity and inflammation following helminth challenge or exposure to allergens. Specifically, recent reports have begun to define the complex cellular networks these alarmins activate and their contribution to type 2 immunity and inflammation. Summary Our increased understanding of the pathways that regulate type 2 cytokine-mediated immunity and inflammation have revealed novel therapeutic targets to treat both helminth infections and allergic disease states.

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“…This heterodimeric cytokine binds to the IL-27 receptor and gp130 to activate STAT1 (33)(34)(35) and induce Th1 cell differentiation (32,36) whereas it directly suppresses Th2 and Th17 differentiation (37). Very recently, it was shown in different models of lung inflammation, including allergic inflammation and viral respiratory tract infection, that IFNs and IL-27 regulate the function of group 2 innate lymphoid cells and thereby together restrict type 2 immune responses (38)(39)(40). Using a model of immune perturbation, Molofsky et al (41) have also shown that a counterregulatory mechanism involving IFN-g and IL-33 is involved in regulating type 2 innate lymphoid cells and thereby maintenance of immune homeostasis.…”

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confidence: 99%

IL-27 Is Essential for Suppression of Experimental Allergic Asthma by the TLR7/8 Agonist R848 (Resiquimod)

Jirmo

Daluege

Happle

et al. 2016

The Journal of Immunology

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Different models of experimental allergic asthma have shown that the TLR7/8 agonist resiquimod (R848) is a potential inhibitor of type 2 helper cell–driven inflammatory responses. However, the mechanisms mediating its therapeutic effects are not fully understood. Using a model of experimental allergic asthma, we show that induction of IL-27 by R848 is critical for the observed ameliorative effects. R848 significantly inhibited all hallmarks of experimental allergic asthma, including airway hyperreactivity, eosinophilic airway inflammation, mucus hypersecretion, and Ag-specific Ig production. Whereas R848 significantly reduced IL-5, IL-13, and IL-17, it induced IFN-γ and IL-27. Neutralization of IL-27 completely reversed the therapeutic effect of R848 in the experimental asthma model, demonstrating dependence of R848-mediated suppression on IL-27. In vitro, R848 induced production of IL-27 by murine alveolar macrophages and dendritic cells and enhanced expression of programmed death–ligand 1, whose expression on monocytes and dendritic cells has been shown to regulate peripheral tolerance in both murine and human studies. Moreover, in vitro IL-27 enhanced secretion of IFN-γ whereas it inhibited IL-5 and IL-13, demonstrating its direct effect on attenuating Th2 responses. Taken together, our study proves that R848-mediated suppression of experimental asthma is dependent on IL-27. These data provide evidence of a central role of IL-27 for the control of Th2-mediated allergic diseases.

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IL-27 suppresses type 2 immune responses in vivo via direct effects on group 2 innate lymphoid cells

Cited by 61 publications

References 55 publications

The group 2 innate lymphoid cell (ILC2) regulatory network and its underlying mechanisms

The group 2 innate lymphoid cell (ILC2) regulatory network and its underlying mechanisms

Type 2 Cytokine Responses: Regulating Immunity to Helminth Parasites and Allergic Inflammation

IL-27 Is Essential for Suppression of Experimental Allergic Asthma by the TLR7/8 Agonist R848 (Resiquimod)

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