Psoriatic T cells recognize neolipid antigens generated by mast cell phospholipase delivered by exosomes and presented by CD1a.
Psoriatic T cells recognize neolipid antigens generated by mast cell phospholipase delivered by exosomes and presented by CD1a.
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DOI：
10.1084/jem.20160258
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发表时间：
2016-10-17
期刊：
影响因子：
--
通讯作者：
Ogg G
中科院分区：
文献类型：
--
作者：
Cheung KL;Jarrett R;Subramaniam S;Salimi M;Gutowska-Owsiak D;Chen YL;Hardman C;Xue L;Cerundolo V;Ogg G
在银屑病中，IFN-α刺激的肥大细胞释放含有细胞质PLA 2的外泌体，其被转移到表达CD 1a的细胞并产生新脂质抗原，所述新脂质抗原诱导CD 1a反应性T细胞产生IL-22和IL-17 A。银屑病是一种与辅助性T细胞17应答相关的慢性炎症性皮肤病。然而，已经证明鉴定相关的基于肽的T细胞抗原具有挑战性。抗原呈递朗格汉斯细胞在银屑病皮损中表现出不同的迁移表型，并表达组成性高水平的CD 1a，其将脂质抗原呈递给T细胞。此外，磷脂酶A2（PLA 2）在银屑病病变中高度表达，并且已知其产生新脂质皮肤抗原以供CD 1a反应性T细胞识别。在这项研究中，我们观察到的表达胞质PLA 2（PLA 2G 4D）在银屑病肥大细胞，但出乎意料的是，也发现PLA 2G 4D的活动是细胞外的。这可以通过IFN-α诱导肥大细胞释放外泌体来解释，外泌体将细胞质PLA 2活性转移到邻近的表达CD 1a的细胞。这导致新脂质抗原的产生，随后被脂质特异性CD 1a反应性T细胞识别，诱导IL-22和IL-17 A的产生。与健康对照组相比，银屑病患者的循环和皮肤来源的T细胞显示出升高的PLA 2G 4D反应性。总的来说，这些数据提出了银屑病发病机制的替代模型，其中脂质特异性CD 1a反应性T细胞有助于银屑病炎症。研究结果表明，PLA 2抑制或CD 1a阻断可能具有治疗银屑病的潜力。
In psoriasis, IFN-α–stimulated mast cells release exosomes containing cytoplasmic PLA2 that are transferred to CD1a-expressing cells and generate neolipid antigens which induce the production of IL-22 and IL-17A by CD1a-reactive T cells. Psoriasis is a chronic inflammatory skin disease associated with a T helper 17 response. Yet, it has proved challenging to identify relevant peptide-based T cell antigens. Antigen-presenting Langerhans cells show a differential migration phenotype in psoriatic lesions and express constitutively high levels of CD1a, which presents lipid antigens to T cells. In addition, phospholipase A2 (PLA2) is highly expressed in psoriatic lesions and is known to generate neolipid skin antigens for recognition by CD1a-reactive T cells. In this study, we observed expression of a cytoplasmic PLA2 (PLA2G4D) in psoriatic mast cells but, unexpectedly, also found PLA2G4D activity to be extracellular. This was explained by IFN-α–induced mast cell release of exosomes, which transferred cytoplasmic PLA2 activity to neighboring CD1a-expressing cells. This led to the generation of neolipid antigens and subsequent recognition by lipid-specific CD1a-reactive T cells inducing production of IL-22 and IL-17A. Circulating and skin-derived T cells from patients with psoriasis showed elevated PLA2G4D responsiveness compared with healthy controls. Overall, these data present an alternative model of psoriasis pathogenesis in which lipid-specific CD1a-reactive T cells contribute to psoriatic inflammation. The findings suggest that PLA2 inhibition or CD1a blockade may have therapeutic potential for psoriasis.
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影响因子：
13.8
作者：
Gelfand, JM;Stern, RS;Margolis, DJ
通讯作者：
Margolis, DJ
DOI：
10.1084/jem.20052367
发表时间：
2006-04-17
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Cumberbatch M;Singh M;Dearman RJ;Young HS;Kimber I;Griffiths CE
通讯作者：
Griffiths CE
影响因子：
10.3
作者：
Dyring-Andersen, B.;Geisler, C.;Bonefeld, C. M.
通讯作者：
Bonefeld, C. M.
影响因子：
4.8
作者：
Chiba, H;Michibata, H;Imai, Y
通讯作者：
Imai, Y
影响因子：
3.6
作者：
Balato, Anna;Lembo, Serena;Ayala, Fabio
通讯作者：
Ayala, Fabio