近日,，國際著名雜志《自然—免疫學(xué)》Nature Immunology在線刊登了瑞士,、中國等國科學(xué)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,，研究者發(fā)現(xiàn)了一類脂肪分子,，為一種獨(dú)特早期應(yīng)答免疫細(xì)胞的發(fā)育所必需,。這種被稱為“不變的自然殺手”（iNKT）的免疫細(xì)胞具有大量分泌細(xì)胞因子和影響其他免疫細(xì)胞應(yīng)答的作用,。
先前研究表明，iNKT細(xì)胞可以識別各種微生物脂肪分子,；但是，發(fā)育中的胸腺iNKT細(xì)胞能識別的自生脂肪分子的種類卻一直存在很多爭議,。
Gennaro De Libero和同事發(fā)現(xiàn)含醚類脂肪分子會選擇胸腺iNKT細(xì)胞,。也就是說,，合成的含醚類脂肪分子會潛在地激活成熟的iNKT細(xì)胞并促進(jìn)胸腺iNKT細(xì)胞的發(fā)育,。
他們還注意到,，如果缺少GNPAT這種能生產(chǎn)含醚類脂肪的酶,，那么小鼠體內(nèi)只會產(chǎn)生很少量的iNKT細(xì)胞并且該細(xì)胞無法在末梢組織中聚積。這項(xiàng)研究有助于進(jìn)一步了解這種含醚類脂肪分子發(fā)育和存活的標(biāo)準(zhǔn)。（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.
