Invariant NKT cells are required for airway inflammation induced by environmental antigens

Wingender, Gerhard; Rogers, Paul; Batzer, Glenda; Lee, Myung Steve; Bai, Dong; Peng, Bo; Khurana, Archana; Kronenberg, Mitchell; Horner, Anthony A.

doi:10.1084/jem.20102229

Cited by 96 publications

(121 citation statements)

References 58 publications

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“…CD1-dependent immunomodulatory lipids have been identified in gut microbes (11,12), pollen (23), house dust (24), and in our work, cow's milk. We have previously demonstrated that cow's milk contains substantially more lipid antigen activity than human or mouse milk.…”

Section: Discussionmentioning

confidence: 50%

Structural determination of lipid antigens captured at the CD1d–T-cell receptor interface

Brennan

Cheng

Pellicci

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

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Glycolipid antigens recognized by αβ T-cell receptors (TCRs) drive the activation of invariant natural killer T (iNKT) cells, a specialized subset of innate T lymphocytes. Glycolipids with α-linked anomeric carbohydrates have been identified as potent microbial lipid antigens for iNKT cells, and their unusual α-anomeric linkage has been thought to define a “foreign” lipid antigen motif. However, mammals use endogenous lipids to select iNKT cells, and there is compelling evidence for iNKT cell responses in various types of sterile inflammation. The nature of endogenous or environmental lipid antigens encountered by iNKT cells is not well defined. Here, we sought to identify lipid antigens in cow’s milk, a prominent part of the human diet. We developed a method to directly capture lipid antigens within CD1d–lipid–TCR complexes, while excluding CD1d bound to nonantigenic lipids, followed by direct biochemical analysis of the lipid antigens trapped at the TCR–CD1d interface. The specific antigens captured by this “TCR trap” method were identified as α-linked monohexosylceramides by mass spectrometry fragmentation patterns that distinguished α- from β-anomeric monohexosylceramides. These data provide direct biochemical evidence for α-linked lipid antigens from a common dietary source.

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Section: Discussionmentioning

confidence: 50%

Structural determination of lipid antigens captured at the CD1d–T-cell receptor interface

Brennan

Cheng

Pellicci

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

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“…Flow cytometry and preparation of fluorochrome-conjugated αGalCer-loaded CD1d tetramers were performed as previously described (71 ) were isolated from spleen using a FACSAria cell sorter (BD Biosciences) and stored as cell pellets at -80°C. RNA was isolated from the frozen cell pellets using the RNeasy Mini Kit (QIAGEN), and…”

Section: Methodsmentioning

confidence: 99%

IL-10–producing NKT10 cells are a distinct regulatory invariant NKT cell subset

Sağ¹,

Krause²,

Hedrick³

et al. 2014

J. Clin. Invest.

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223

269

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“…Similarly, 5 × 10 5 /ml DCs, DCs-αGC, or DCs-αGC-ATL313 were cocultured with Vα14Vβ8.2 NKT cell DN3A4-1.2 hybridomas (1.2) in 96-well round-bottom plates, and supernatant IL-2 was measured by ELISA (eBioscience) according to published protocols (70). αGC-or αGC-ATL313-loaded B cells (A20) were also cocultured with NKT cells to test NKT cell response by measuring IL-2 levels.…”

Section: Or Moderate [28 Minutes] Ischemic Injury)mentioning

confidence: 99%

Dendritic cells tolerized with adenosine A2AR agonist attenuate acute kidney injury

Huang²,

Ye³

et al. 2012

J. Clin. Invest.

142

123

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Invariant NKT cells are required for airway inflammation induced by environmental antigens

Abstract: House dust contains antigens capable of activating mouse and human iNKT cells, contributing to allergen-induced airway inflammation.

Cited by 96 publications

References 58 publications

Structural determination of lipid antigens captured at the CD1d–T-cell receptor interface

Structural determination of lipid antigens captured at the CD1d–T-cell receptor interface

IL-10–producing NKT10 cells are a distinct regulatory invariant NKT cell subset

Dendritic cells tolerized with adenosine A2AR agonist attenuate acute kidney injury

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