CD200–CD200R immune checkpoint engagement regulates ILC2 effector function and ameliorates lung inflammation in asthma

Shafiei-Jahani, Pedram; Helou, Doumet Georges; Hurrell, Benjamin P.; Howard, Emily; Quach, Christine; Painter, Jacob D.; Galle-Treger, Lauriane; Li, Meng; Loh, Yong-Hwee Eddie; Akbari, Omid

doi:10.1038/s41467-021-22832-7

Cited by 28 publications

(21 citation statements)

References 44 publications

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“…Initially, we utilized the A. alternata-based model of allergic airway inflammation because A. alternata is commonly found in the environment and is a well-known allergen in humans (45,53). A. alternata has been reported to cause allergic inflammation in mice independent of adaptive immunity, making it an ideal model for studying ILC2-dependent asthma (12,29). We subsequently utilized an IL-33-based model of allergic airway inflammation because IL-33 and IL-25 have been previously shown to induce ILC2-mediated lung inflammation and IL-33 is more potent than IL-25 (54)(55)(56).…”

Section: Discussionmentioning

confidence: 99%

“…Briefly, the following semiquantitative scoring was used: 0-4: 0, none; 1, mild; 2, moderate; 3, marked; and 4, severe. An increment of 0.5 was used when the inflammation fell between two levels (29,45). Besides, infiltrating cells numbers and the epithelial thickness of each individual airway were also measured as reported previously (29).…”

Section: Histological Analysis Of the Lungsmentioning

confidence: 99%

“…An increment of 0.5 was used when the inflammation fell between two levels (29,45). Besides, infiltrating cells numbers and the epithelial thickness of each individual airway were also measured as reported previously (29).…”

Section: Histological Analysis Of the Lungsmentioning

confidence: 99%

“…ILC2s also express cysteinyl leukotriene receptor 1 (CysLT1R), and leukotrienes promote ILC2 activation, which can be blocked by a CysLT1R antagonist (25)(26)(27)(28). Besides, CD200R mediates ILC2 regulation in asthma, and can be blocked in the same manner (29). Hence, blocking receptors expressed by ILC2 might potentially inhibit ILC2 function in allergic airway inflammation.…”

Section: Introductionmentioning

confidence: 99%

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Endothelin-A Receptor Antagonist Alleviates Allergic Airway Inflammation via the Inhibition of ILC2 Function

et al. 2022

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Allergic airway inflammation is a universal airway disease that is driven by hyperresponsiveness to inhaled allergens. Group 2 innate lymphoid cells (ILC2s) produce copious amounts of type 2 cytokines, which lead to allergic airway inflammation. Here, we discovered that both peripheral blood of human and mouse lung ILC2s express the endothelin-A receptor (ETAR), and the expression level of ETAR was dramatically induced upon interleukin-33 (IL-33) treatment. Subsequently, both preventive and therapeutic effects of BQ123, an ETAR antagonist, on allergic airway inflammation were observed, which were associated with decreased proliferation and type 2 cytokine productions by ILC2s. Furthermore, ILC2s from BQ123 treatment were found to be functionally impaired in response to an interleukin IL-33 challenged. And BQ123 treatment also affected the phosphorylation level of the extracellular signal-regulated kinase (ERK), as well as the level of GATA binding protein 3 (GATA3) in activated ILC2s. Interestingly, after BQ123 treatment, both mouse and human ILC2s in vitro exhibited decreased function and downregulation of ERK signaling and GATA3 stability. These observations imply that ETAR is an important regulator of ILC2 function and may be involved in ILC2-driven pulmonary inflammation. Therefore, blocking ETAR may be a promising therapeutic strategy for allergic airway inflammation.

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Section: Discussionmentioning

confidence: 99%

Section: Histological Analysis Of the Lungsmentioning

confidence: 99%

Section: Histological Analysis Of the Lungsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Endothelin-A Receptor Antagonist Alleviates Allergic Airway Inflammation via the Inhibition of ILC2 Function

et al. 2022

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“…1d ). We also compared NmUR1 expression in different subsets of ILC2s 22 , 23 , but no significant difference was detected (Fig. 1e ).…”

Section: Resultsmentioning

confidence: 93%

Neuromedin U promotes human type 2 immune responses

et al. 2022

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Type 2 immunity mediates the immune responses against parasites and allergic stimuli. Evidence from studies of cell lines and animals implies that neuromedin U (NmU) acts as a pro-inflammatory mediator of type 2 inflammation. However, the role of NmU in human type 2 immunity remains unclear. Here we investigated the expression of NmU in human blood and airways, and the expression of NmU receptors by human immune cells in blood and lung tissue. We detected human NmU (hNmU-25) in blood and airways with higher concentrations in the latter. NmU receptor 1 (NmUR1) was expressed by most human immune cells with higher levels in type 2 cells including type 2 T helpers, type 2 cytotoxic T cells, group-2 innate lymphoid cells and eosinophils, and was upregulated in lung-resident and activated type 2 cells. We also assessed the effects of NmU in these cells. hNmU-25 elicited type 2 cytokine production by type 2 lymphocytes and induced cell migration, including eosinophils. hNmU-25 also enhanced the type 2 immune response to other stimuli, particularly prostaglandin D2. These results indicate that NmU could contribute to the pathogenic processes of type 2 immunity-mediated diseases in humans via its pro-inflammatory effects on type 2 lymphocytes and eosinophils.

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Guidelines for the use of flow cytometry and cell sorting in immunological studies (third edition)

et al. 2021

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The third edition of Flow Cytometry Guidelines provides the key aspects to consider when performing flow cytometry experiments and includes comprehensive sections describing phenotypes and functional assays of all major human and murine immune cell subsets. Notably, the Guidelines contain helpful tables highlighting phenotypes and key differences between human and murine cells. Another useful feature of this edition is the flow cytometry analysis of clinical samples with examples of flow cytometry applications in the context of autoimmune diseases, cancers as well as acute and chronic infectious diseases. Furthermore, there are sections detailing tips, tricks and pitfalls to avoid. All sections are written and peer-reviewed by leading flow cytometry experts and immunologists, making this edition an essential and state-of-the-art handbook for basic and clinical researchers.

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CD200–CD200R immune checkpoint engagement regulates ILC2 effector function and ameliorates lung inflammation in asthma

Cited by 28 publications

References 44 publications

Endothelin-A Receptor Antagonist Alleviates Allergic Airway Inflammation via the Inhibition of ILC2 Function

Endothelin-A Receptor Antagonist Alleviates Allergic Airway Inflammation via the Inhibition of ILC2 Function

Neuromedin U promotes human type 2 immune responses

Guidelines for the use of flow cytometry and cell sorting in immunological studies (third edition)

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