Nat Immun：发现iNKT免疫细胞发育所需的脂肪分子

近日，国际著名杂志《自然—免疫学》Nature Immunology在线刊登了瑞士、中国等国科学家合作的研究成果“Peroxisome-derived lipids are self antigens that stimulate invariant natural killer T cells in the thymus，”，在文章中，研究者发现了一类脂肪分子，为一种独特早期应答免疫细胞的发育所必需。这种被称为“不变的自然杀手”（iNKT）的免疫细胞具有大量分泌细胞因子和影响其他免疫细胞应答的作用。

先前研究表明，iNKT细胞可以识别各种微生物脂肪分子；但是，发育中的胸腺iNKT细胞能识别的自生脂肪分子的种类却一直存在很多争议。

Gennaro De Libero和同事发现含醚类脂肪分子会选择胸腺iNKT细胞。也就是说，合成的含醚类脂肪分子会潜在地激活成熟的iNKT细胞并促进胸腺iNKT细胞的发育。

他们还注意到，如果缺少GNPAT这种能生产含醚类脂肪的酶，那么小鼠体内只会产生很少量的iNKT细胞并且该细胞无法在末梢组织中聚积。这项研究有助于进一步了解这种含醚类脂肪分子发育和存活的标准。（生物谷Bioon.com）

doi:10.1038/ni.2245
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Peroxisome-derived lipids are self antigens that stimulate invariant natural killer T cells in the thymus

Federica Facciotti,1, 5 Gundimeda S Ramanjaneyulu,1 Marco Lepore,1 Sebastiano Sansano,1 Marco Cavallari,1 Magdalena Kistowska,1, 5 Sonja Forss-Petter,2 Guanghui Ni,3 Alessia Colone,4 Amit Singhal,4 Johannes Berger,2 Chengfeng Xia,3 Lucia Mori1, 4 & Gennaro De Libero1, 4

The development and maturation of semi-invariant natural killer T cells (iNKT cells) rely on the recognition of self antigens presented by CD1d restriction molecules in thymus. The nature of the stimulatory thymic self lipids remains elusive. We isolated lipids from thymocytes and found that ether-bonded mono-alkyl glycerophosphates and the precursors and degradation products of plasmalogens stimulated iNKT cells. Synthetic analogs showed high potency in activating thymic and peripheral iNKT cells. Mice deficient in the peroxisomal enzyme glyceronephosphate O-acyltransferase (GNPAT), essential for the synthesis of ether lipids, had significant alteration of the thymic maturation of iNKT cells and fewer iNKT cells in both thymus and peripheral organs, which confirmed the role of ether-bonded lipids as iNKT cell antigens. Thus, peroxisome-derived lipids are nonredundant self antigens required for the generation of a full iNKT cell repertoire.