Olea europaea pollen lipids activate invariant natural killer T cells by upregulating CD1d expression on dendritic cells

Abós-Gracia, Beatriz; Moral, Manuel Gómez del; López-Relaño, Juan; Viana-Huete, Vanesa; Castro, Lorena Amaro; Villalba, Mayte; Martı́nez-Naves, Eduardo

doi:10.1016/j.jaci.2012.11.014

Cited by 25 publications

(28 citation statements)

References 34 publications

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“…The levels of CD1d were comparable to those observed after treating the cells with ATRA (Fig. 2a, b), an agent known to enhance the CD1d cell surface expression on DCs [7,9]. When the total-lipid extract was fractionated, we found an increase of CD1d expression on cells treated with both polar and apolar lipid fractions (Fig.…”

Section: Resultssupporting

confidence: 79%

“…The relative mobility of each band was used to identify crude fractions: polar lipids, diacylglycerols, free fatty acids and triacylglycerols. Total and polar lipids were quantified by a phosphorous assay [7]. …”

Section: Methodsmentioning

confidence: 99%

“…After exposure to the lipids, DCs upregulate CD1d and CD86 molecules on their cell surface and activate iNKT cells through a CD1d-dependent pathway, suggesting that lipids can influence the immune response against pollen antigens [7]. …”

Section: Introductionmentioning

confidence: 99%

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Human Invariant Natural Killer T Cells Respond to Antigen-Presenting Cells Exposed to Lipids from Olea europaea Pollen

Gracia

López-Relaño²,

Revilla³

et al. 2017

Int Arch Allergy Immunol

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Background: Allergic sensitization might be influenced by the lipids present in allergens, which can be recognized by natural killer T (NKT) cells on antigen-presenting cells (APCs). The aim of this study wasto analyze the effect of olive pollen lipids in human APCs, including monocytes as well as monocyte-derived macrophages (Mϕ) and dendritic cells (DCs). Methods: Lipids were extracted from olive (Olea europaea) pollen grains. Invariant (i)NKT cells, monocytes, Mϕ, and DCs were obtained from buffy coats of healthy blood donors, and their cell phenotype was determined by flow cytometry. iNKT cytotoxicity was measured using a lactate dehydrogenase assay. Gene expression of CD1A and CD1D was performed by RT-PCR, and the production of IL-6, IL-10, IL-12, and TNF-α cytokines by monocytes, Mϕ, and DCs was measured by ELISA. Results: Our results showed that monocytes and monocyte-derived Mϕ treated with olive pollen lipids strongly activate iNKT cells. We observed several phenotypic modifications in the APCs upon exposure to pollen-derived lipids. Both Mϕ and monocytes treated with olive pollen lipids showed an increase in CD1D gene expression, whereas upregulation of cell surface CD1d protein occurred only in Mϕ. Furthermore, DCs differentiated in the presence of human serum enhance their surface CD1d expression when exposed to olive pollen lipids. Finally, olive pollen lipids were able to stimulate the production of IL-6 but downregulated the production of lipopolysaccharide- induced IL-10 by Mϕ. Conclusions: Olive pollen lipids alter the phenotype of monocytes, Mϕ, and DCs, resulting in the activation of NKT cells, which have the potential to influence allergic immune responses.

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Section: Resultssupporting

confidence: 79%

Section: Methodsmentioning

confidence: 99%

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Human Invariant Natural Killer T Cells Respond to Antigen-Presenting Cells Exposed to Lipids from Olea europaea Pollen

Gracia

López-Relaño²,

Revilla³

et al. 2017

Int Arch Allergy Immunol

Self Cite

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“…64 However, it should be noted that some preliminary data suggest that plants and their pollen might contain iNKT cell antigens as well. [83][84][85] Altogether, recent findings indicate that antigens for iNKT cells are almost ubiquitous indoors and in the environment. As they will reach the airways with the inhaled air, it seems likely that iNKT cell antigens are present under normal conditions in the lung at low levels and could under certain conditions contribute to airway inflammation.…”

Section: Inkt Cells and The Microbiota In The Respiratory Tractmentioning

confidence: 98%

The interaction between invariant Natural Killer T cells and the mucosal microbiota

Hapil¹,

Wingender

2018

Immunology

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SummaryThe surface of mammalian bodies is colonized by a multitude of microbial organisms, which under normal conditions support the host and are considered beneficial commensals. This requires, however, that the composition of the commensal microbiota is tightly controlled and regulated. The host immune system plays an important role in the maintenance of this microbiota composition. Here we focus on the contribution of one particular immune cell type, invariant Natural Killer T (iNKT) cells, in this process. The iNKT cells are a unique subset of T cells characterized by two main features. First, they express an invariant T-cell receptor that recognizes glycolipid antigens presented by CD1d, a non-polymorphic major histocompatibility complex class I-like molecule. Second, iNKT cells develop as effector/memory cells and swiftly exert effector functions, like cytokine production and cytotoxicity, after activation. We outline the influence that the mucosal microbiota can have on iNKT cells, and how iNKT cells contribute to the maintenance of the microbiota composition.

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“…However, a number of lines of evidence suggest that the epitope bound by NIB.2 is recognized when a variety of lipid antigens are present in complex with CD1d: (1) NIB.2 binds to CD1d on transfected HEK cells and native CD1d on human PBMCs (Fig. 1B) -these cells would be expected to present a diverse array of lipids; 16,23 (2) NIB.2 neutralizes NKT cell cytokine release activity mediated by CD1d C cells loaded with 2 different glycolipids (Fig. 2); and (3) epitope mapping, as described below.…”

Section: Characterization Of the Nib2 Epitope On Human Cd1dmentioning

confidence: 99%

Potent neutralizing anti-CD1d antibody reduces lung cytokine release in primate asthma model

Nambiar

Clarke²,

Shim³

et al. 2015

mAbs

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(2015) Potent neutralizing anti-CD1d antibody reduces lung cytokine release in primate asthma model, mAbs, 7:3, 638-650, DOI: 10.1080/19420862.2015 To link to this article: https://doi.org/10. 1080/19420862.2015 Keywords: CD1d, NKT cell, antibody, asthma, cytokineAbbreviations: AHR, airway hyper-reactivity; APC, antigen-presenting cell; AUC, area under the curve; BAL, broncho-alveolar lavage; BSA, bovine serum albumin; CHO, Chinese hamster ovary; ELISA, enzyme-linked immunosorbent assay; G-CSF, granulocyte colony stimulating factor; GM-CSF, granulocyte-macrophage colony stimulating factor; HEK, human embryonic kidney; HPLC, high performance liquid chromatography; IFN, interferon; IL, interleukin; MCh, methacholine; MHC, major histocompatibility complex; MIP, macrophage inflammatory protein; NKT, natural killer T; OVA, ovalbumin; PBMC, peripheral blood mononuclear cell; PBS, phosphate-buffered saline; SDS-PAGE, sodium dodecyl sulfate-polyacrylamide gel electrophoresis; SPR, surface plasmon resonance; TNF, tumor necrosis factor; VEGF, vascular endothelial growth factorCD1d is a receptor on antigen-presenting cells involved in triggering cell populations, particularly natural killer T (NKT) cells, to release high levels of cytokines. NKT cells are implicated in asthma pathology and blockade of the CD1d/ NKT cell pathway may have therapeutic potential. We developed a potent anti-human CD1d antibody (NIB.2) that possesses high affinity for human and cynomolgus macaque CD1d (K D »100 pM) and strong neutralizing activity in human primary cell-based assays (IC 50 typically <100 pM). By epitope mapping experiments, we showed that NIB.2 binds to CD1d in close proximity to the interface of CD1d and the Type 1 NKT cell receptor b-chain. Together with data showing that NIB.2 inhibited stimulation via CD1d loaded with different glycolipids, this supports a mechanism whereby NIB.2 inhibits NKT cell activation by inhibiting Type 1 NKT cell receptor b-chain interactions with CD1d, independent of the lipid antigen in the CD1d antigen-binding cleft. The strong in vitro potency of NIB.2 was reflected in vivo in an Ascaris suum cynomolgus macaque asthma model. Compared with vehicle control, NIB.2 treatment significantly reduced bronchoalveolar lavage (BAL) levels of Ascaris-induced cytokines IL-5, IL-8 and IL-1 receptor antagonist, and significantly reduced baseline levels of GM-CSF, IL-6, IL-15, IL-12/23p40, MIP-1a, MIP-1b, and VEGF. At a cellular population level NIB.2 also reduced numbers of BAL lymphocytes and macrophages, and blood eosinophils and basophils. We demonstrate that anti-CD1d antibody blockade of the CD1d/NKT pathway modulates inflammatory parameters in vivo in a primate inflammation model, with therapeutic potential for diseases where the local cytokine milieu is critical.

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Olea europaea pollen lipids activate invariant natural killer T cells by upregulating CD1d expression on dendritic cells

Cited by 25 publications

References 34 publications

Human Invariant Natural Killer T Cells Respond to Antigen-Presenting Cells Exposed to Lipids from Olea europaea Pollen

Human Invariant Natural Killer T Cells Respond to Antigen-Presenting Cells Exposed to Lipids from Olea europaea Pollen

The interaction between invariant Natural Killer T cells and the mucosal microbiota

Potent neutralizing anti-CD1d antibody reduces lung cytokine release in primate asthma model

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