Neuropilin-1 mediates lung tissue-specific control of ILC2 function in type 2 immunity

Zhang, Jingjing; Qiu, Jinxin; Zhou, Wenyong; Cao, Jianping; Hu, Xuefei; Mi, Wen-Li; Su, Bing; He, Binglin; Qiu, Ju; Shen, Lei

doi:10.1038/s41590-021-01097-8

Cited by 43 publications

(38 citation statements)

References 49 publications

(64 reference statements)

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“…Some, if only a small proportion, of the gut ILC2s that enter the lungs upregulate expression of the IL-33 receptor ST2 (also known as IL-1RL1), thereby taking on the phenotype of lung-resident ILC2s (also referred to as ‘natural’ ILC2s) (Table 2 ). It is currently unclear if gut ILC2s that enter the lung during N. brasiliensis infection also upregulate neuropilin 1 (NRP1), which was recently shown to be an activating receptor specifically expressed by lung ILC2s and upregulated on intestinal ILC2s following transfer to the lungs in mice 41 . In addition to the influx of gut ILC2s, recruited and tissue-resident precursors of ILC2s also contribute to the local population of ILC2s in the lung and have a role in the dynamic diversity of ILC2s observed in the lung during N. brasiliensis infection 42 .…”

Section: Ilc2 Tissue Residency and Migrationmentioning

confidence: 99%

Heterogeneity of type 2 innate lymphoid cells

Spits

Mjösberg

2022

Nat Rev Immunol

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More than a decade ago, type 2 innate lymphoid cells (ILC2s) were discovered to be members of a family of innate immune cells consisting of five subsets that form a first line of defence against infections before the recruitment of adaptive immune cells. Initially, ILC2s were implicated in the early immune response to parasitic infections, but it is now clear that ILC2s are highly diverse and have crucial roles in the regulation of tissue homeostasis and repair. ILC2s can also regulate the functions of other type 2 immune cells, including T helper 2 cells, type 2 macrophages and eosinophils. Dysregulation of ILC2s contributes to type 2-mediated pathology in a wide variety of diseases, potentially making ILC2s attractive targets for therapeutic interventions. In this Review, we focus on the spectrum of ILC2 phenotypes that have been described across different tissues and disease states with an emphasis on human ILC2s. We discuss recent insights in ILC2 biology and suggest how this knowledge might be used for novel disease treatments and improved human health.

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Section: Ilc2 Tissue Residency and Migrationmentioning

confidence: 99%

Heterogeneity of type 2 innate lymphoid cells

Spits

Mjösberg

2022

Nat Rev Immunol

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“…It suggested TGF-β can promote the expression of Nrp-1 in iTreg based on TCR and IL-2 signaling. Recent studies demonstrated that TGF-β can also promote the expression of Nrp-1 in lung type II innate lymphoid cells (ILC2) ( 30 ). TGF-β can induce the expression of transcription factor SP1 ( 31 ), which can upregulate Nrp-1 expression by binding to the Nrp-1 promoter ( 32 ).…”

Section: Discussionmentioning

confidence: 99%

Neuropilin-1 Identifies a New Subpopulation of TGF-β-Induced Foxp3+ Regulatory T Cells With Potent Suppressive Function and Enhanced Stability During Inflammation

et al. 2022

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CD4+Foxp3+ regulatory T cells (Tregs) play a crucial role in preventing autoimmunity and inflammation. There are naturally-derived in the thymus (tTreg), generated extrathymically in the periphery (pTreg), and induced in vitro culture (iTreg) with different characteristics of suppressiveness, stability, and plasticity. There is an abundance of published data on neuropilin-1 (Nrp-1) as a tTreg marker, but little data exist on iTreg. The fidelity of Nrp-1 as a tTreg marker and its role in iTreg remains to be explored. This study found that Nrp-1 was expressed by a subset of Foxp3+CD4+T cells in the central and peripheral lymphoid organs in intact mice, as well as in iTreg. Nrp-1+iTreg and Nrp-1-iTreg were adoptively transferred into a T cell-mediated colitis model to determine their ability to suppress inflammation. Differences in gene expression between Nrp-1+ and Nrp-1-iTreg were analyzed by RNA sequencing. We demonstrated that the Nrp-1+ subset of the iTreg exhibited enhanced suppressive function and stability compared to the Nrp-1- counterpart both in vivo and in vitro, partly depending on IL-10. We found that Nrp-1 is not an exclusive marker of tTreg, however, it is a biomarker identifying a new subset of iTreg with enhanced suppressive function, implicating a potential for Nrp-1+iTreg cell therapy for autoimmune and inflammatory diseases.

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“…For example, Helou et al adoptively transferred in vitro cultured human ILC2s into Rag2 −/− Il2rg −/− mice, followed by PD-1 agonist administration, to study the role of PD-1 in human ILC2s [ 39 ]; Howard et al sorted ILC2s from IL-33-treated PD-1 knockout mice and transferred them into Rag2 −/− Il2rg −/− mice to evaluate PD-1 function in ILC2s [ 40 ]. Moreover, Nussbaum et al generated reporter mice Red5 (recombinase-expressing detector for IL-5, R5) [ 41 ], and the R5/+ mice have been widely used to construct ILC2-specific gene deletion models [ 42 , 43 ]. Hence, further studies are necessary to ascertain the intrinsic role of CD226 in ILC2s.…”

Section: Discussionmentioning

confidence: 99%

CD226 Deficiency Alleviates Murine Allergic Rhinitis by Suppressing Group 2 Innate Lymphoid Cell Responses

Xie

Zhang

Zhu

et al. 2022

Mediators of Inflammation

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Allergic rhinitis (AR) is an immunoglobulin E-mediated type 2 inflammation of the nasal mucosa that is mainly driven by type 2 helper T cells (Th2) and type 2 innate lymphoid cells (ILC2s). CD226 is a costimulatory molecule associated with inflammatory response and is mainly expressed on T cells, natural killer cells, and monocytes. This study is aimed at elucidating the role of CD226 in allergic inflammatory responses in murine AR using global and CD4+ T cell-specific Cd226 knockout (KO) mice. AR nasal symptoms were assessed based on the frequency of nose rubbing and sneezing. Hematoxylin and eosin and periodic acid–Schiff staining and quantitative real-time PCR methods were used to determine eosinophils, goblet cells, and ILC2-associated mRNA levels in the nasal tissues of mice. CD226 levels on ILC2s were detected using flow cytometry, and an immunofluorescence double staining assay was employed to determine the number of ILC2s in the nasal mucosa. The results showed that global Cd226 KO mice, but not CD4+ T cell-specific Cd226 KO mice, exhibited attenuated AR nasal symptoms. Eosinophil recruitment, goblet cell proliferation, and Th2-inflammatory cytokines were significantly reduced, which resulted in the alleviation of allergic and inflammatory responses. ILC2s in the murine nasal mucosa expressed higher levels of CD226 after ovalbumin stimulation, and CD226 deficiency led to a reduction in the proportion of nasal ILC2s and ILC2-related inflammatory gene expression. Hence, the effect of CD226 on the AR mouse model may involve the regulation of ILC2 function rather than CD4+ T cells.

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Neuropilin-1 mediates lung tissue-specific control of ILC2 function in type 2 immunity

Cited by 43 publications

References 49 publications

Heterogeneity of type 2 innate lymphoid cells

Heterogeneity of type 2 innate lymphoid cells

Neuropilin-1 Identifies a New Subpopulation of TGF-β-Induced Foxp3+ Regulatory T Cells With Potent Suppressive Function and Enhanced Stability During Inflammation

CD226 Deficiency Alleviates Murine Allergic Rhinitis by Suppressing Group 2 Innate Lymphoid Cell Responses

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