Helminthic dehydrogenase drives PGE(2) and IL-10 production in monocytes to potentiate Treg induction.
Helminthic dehydrogenase drives PGE(2) and IL-10 production in monocytes to potentiate Treg induction.
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蠕虫脱氢酶驱动单核细胞产生PGE（2）和IL-10以增强Treg诱导。
DOI：
10.15252/embr.202154096
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发表时间：
2022-05-04
期刊：
影响因子：
7.7
通讯作者：
da Costa, Clarissa Prazeres
中科院分区：
文献类型：
--
作者：
Prodjinotho, Ulrich Fabien;Gres, Vitka;Henkel, Fiona;Lacorcia, Matthew;Dandl, Ramona;Haslbeck, Martin;Schmidt, Veronika;Winkler, Andrea Sylvia;Sikasunge, Chummy;Jakobsson, Per-Johan;Henneke, Philipp;Bieren, Julia Esser-von;da Costa, Clarissa Prazeres
大脑中炎症、感染触发的过程的免疫调节构成了控制癫痫等破坏性疾病表现的核心机制。观察研究表明，猪带绦虫包囊的生存能力是决定脑囊虫病(NCC)严重程度的关键因素，NCC是撒哈拉以南非洲最常见的癫痫原因，尤其是在儿童中。可存活的，与腐烂的相反，由于尚不清楚的机制，囊肿在临床上大多保持沉默，可能涉及Tregs控制炎症。在这里，我们展示了来自活的包囊的谷氨酸脱氢酶指示耐受性单核细胞释放IL-10和脂质介质PGE2。它们协同作用，通过G蛋白偶联受体EP2和EP4以及IL-10受体，将初始的CD+T细胞转化为CD127CD25hiFoxP3+CTLA-4+Treg。−CD25hiFoxP3+CTLA-4+Treg。此外，尽管有活性的囊泡产物强烈上调小胶质细胞中IL-10和PGE_2的转录，但在囊变过程中释放的囊腔内液体会诱导促炎的小胶质细胞和转化生长因子-β作为癫痫的潜在驱动因素。抑制PGE2合成和IL-10信号转导可阻止活性包囊产物对Treg的诱导。利用PGE2-IL-10轴和靶向转化生长因子-β信号转导可能为炎症性癫痫和NCC提供重要的治疗策略。代谢酶谷氨酸脱氢酶存在于成活的蠕虫幼虫包囊中，介导PGE2-IL-10轴的调节性T细胞诱导，从而潜在地控制脑部炎症。
Immunoregulation of inflammatory, infection‐triggered processes in the brain constitutes a central mechanism to control devastating disease manifestations such as epilepsy. Observational studies implicate the viability of Taenia solium cysts as key factor determining severity of neurocysticercosis (NCC), the most common cause of epilepsy, especially in children, in Sub‐Saharan Africa. Viable, in contrast to decaying, cysts mostly remain clinically silent by yet unknown mechanisms, potentially involving Tregs in controlling inflammation. Here, we show that glutamate dehydrogenase from viable cysts instructs tolerogenic monocytes to release IL‐10 and the lipid mediator PGE2. These act in concert, converting naive CD4+ T cells into CD127−CD25hiFoxP3+CTLA‐4+ Tregs, through the G protein‐coupled receptors EP2 and EP4 and the IL‐10 receptor. Moreover, while viable cyst products strongly upregulate IL‐10 and PGE2 transcription in microglia, intravesicular fluid, released during cyst decay, induces pro‐inflammatory microglia and TGF‐β as potential drivers of epilepsy. Inhibition of PGE2 synthesis and IL‐10 signaling prevents Treg induction by viable cyst products. Harnessing the PGE2‐IL‐10 axis and targeting TGF‐ß signaling may offer an important therapeutic strategy in inflammatory epilepsy and NCC. The metabolic enzyme glutamate dehydrogenase, present in viable helminth larval cysts, mediates a PGE2‐IL‐10 axis of regulatory T cell induction, thereby potentially controlling brain inflammation.
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影响因子：
13.6
作者：
Crittenden S;Goepp M;Pollock J;Robb CT;Smyth DJ;Zhou Y;Andrews R;Tyrrell V;Gkikas K;Adima A;O'Connor RA;Davies L;Li XF;Yao HX;Ho GT;Zheng X;Mair A;Vermeren S;Qian BZ;Mole DJ;Gerasimidis K;Schwarze JKJ;Breyer RM;Arends MJ;O'Donnell VB;Iredale JP;Anderton SM;Narumiya S;Maizels RM;Rossi AG;Howie SE;Yao C
通讯作者：
Yao C
影响因子：
8.8
作者：
Bhattacharjee, Sonakshi;Mejias-Luque, Raquel;da Costa, Clarissa Prazeres
通讯作者：
da Costa, Clarissa Prazeres
DOI：
10.1084/jem.20100793
发表时间：
2011-03-14
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Barrett NA;Rahman OM;Fernandez JM;Parsons MW;Xing W;Austen KF;Kanaoka Y
通讯作者：
Kanaoka Y
影响因子：
4.6
作者：
Arce-Sillas, A.;Alvarez-Luquin, D. D.;Adalid-Peralta, L.
通讯作者：
Adalid-Peralta, L.
影响因子：
5.4
作者：
Cardenas, Graciela;Fragoso, Gladis;Fleury, Agnes
通讯作者：
Fleury, Agnes