Indoleamine 2,3-dioxygenase 1 activation in mature cDC1 promotes tolerogenic education of inflammatory cDC2 via metabolic communication.
Indoleamine 2,3-dioxygenase 1 activation in mature cDC1 promotes tolerogenic education of inflammatory cDC2 via metabolic communication.
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DOI：
10.1016/j.immuni.2022.05.013
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发表时间：
2022-06-14
期刊：
影响因子：
32.4
通讯作者：
Fallarino, Francesca
中科院分区：
文献类型：
--
作者：
Gargaro, Marco;Scalisi, Giulia;Manni, Giorgia;Briseno, Carlos G.;Bagadia, Prachi;Durai, Vivek;Theisen, Derek J.;Kim, Sunkyung;Castelli, Marilena;Xu, Chenling A.;zu Horste, Gerd Meyer;Servillo, Giuseppe;Della Fazia, Maria A.;Mencarelli, Giulia;Ricciuti, Doriana;Padiglioni, Eleonora;Giacche, Nicola;Colliva, Carolina;Pellicciari, Roberto;Calvitti, Mario;Zelante, Teresa;Fuchs, Dietmar;Orabona, Ciriana;Boon, Louis;Bessede, Alban;Colonna, Marco;Puccetti, Paolo;Murphy, Theresa L.;Murphy, Kenneth M.;Fallarino, Francesca
传统的树突状细胞（cDC），cDC 1和cDC 2，既能启动免疫，又能维持自身耐受。色氨酸代谢酶吲哚胺2，3-双加氧酶1（IDO 1）被cDC用于维持耐受性，但其在不同亚群中的作用仍不清楚。在稳态时，只有成熟的CCR 7 + cDC 1表达依赖于IRF 8的IDO 1。脂多糖处理诱导成熟和IDO 1依赖性的耐受性活动，在孤立的未成熟的cDC 1，但不是孤立的cDC 2。然而，当与成熟cDC 1共培养时，人和小鼠cDC 2都可以通过cDC 1衍生的l-犬尿氨酸的作用诱导IDO 1并获得致耐受性功能。因此，IDO 1在体内的cDC 1特异性失活加重了实验性自身免疫性脑脊髓炎的疾病。这项研究确定了一种以前未被认识到的代谢通讯，其中IDO 1表达的cDC 1细胞通过产生色氨酸代谢物l-犬尿氨酸将其免疫调节能力扩展到cDC 2亚群。该代谢轴代表了治疗自身免疫性脱髓鞘疾病的潜在治疗靶点。致耐受性IDO 1途径在成熟cDC 1中表达，但在cDC 2中不表达。成熟IDO 1 + cDC 1在体外和体内是调节性的，IDO 1感受态cDC 1通过Trp代谢诱导调节性cDC 2，1-犬尿氨酸将AhR感受态cDC 2募集到致耐受性库中。色氨酸代谢酶吲哚胺2，3-双加氧酶1（IDO 1）的活化诱导DC耐受性，但目前尚不清楚该途径如何被选定的cDC亚群使用。Gargaro等人显示IDO 1途径（其在成熟cDC 1中表达而在cDC 2中不表达）的激活通过AhR介导的代谢通讯诱导调节性cDC 2。
Conventional dendritic cells (cDCs), cDC1 and cDC2, act both to initiate immunity and maintain self-tolerance. The tryptophan metabolic enzyme indoleamine 2,3-dioxygenase 1 (IDO1) is used by cDCs in maintaining tolerance, but its role in different subsets remains unclear. At homeostasis, only mature CCR7+ cDC1 expressed IDO1 that was dependent on IRF8. Lipopolysaccharide treatment induced maturation and IDO1-dependent tolerogenic activity in isolated immature cDC1, but not isolated cDC2. However, both human and mouse cDC2 could induce IDO1 and acquire tolerogenic function when co-cultured with mature cDC1 through the action of cDC1-derived l-kynurenine. Accordingly, cDC1-specific inactivation of IDO1 in vivo exacerbated disease in experimental autoimmune encephalomyelitis. This study identifies a previously unrecognized metabolic communication in which IDO1-expressing cDC1 cells extend their immunoregulatory capacity to the cDC2 subset through their production of tryptophan metabolite l-kynurenine. This metabolic axis represents a potential therapeutic target in treating autoimmune demyelinating diseases. The tolerogenic IDO1 pathway is expressed in mature cDC1 but not in cDC2 Mature IDO1+ cDC1 are regulatory in vitro and in vivo IDO1 competent cDC1 induce regulatory cDC2 via Trp metabolism l-kynurenine recruits AhR competent cDC2 into a tolerogenic pool Activation of the tryptophan metabolic enzyme indoleamine 2,3-dioxygenase 1 (IDO1) induces DC tolerance, but how this pathway is used by selected cDC subsets is currently unclear. Gargaro et al. show that activation of the IDO1 pathway, which is expressed in mature cDC1 but not in cDC2, induces regulatory cDC2 via AhR-mediated metabolic communication.
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DOI：
10.1073/pnas.1619863114
发表时间：
2017-04-11
影响因子：
11.1
作者：
Briseno, Carlos G.;Gargaro, Marco;Murphy, Kenneth M.
通讯作者：
Murphy, Kenneth M.
影响因子：
30.5
作者：
Grajales-Reyes GE;Iwata A;Albring J;Wu X;Tussiwand R;Kc W;Kretzer NM;Briseño CG;Durai V;Bagadia P;Haldar M;Schönheit J;Rosenbauer F;Murphy TL;Murphy KM
通讯作者：
Murphy KM
影响因子：
3.7
作者：
Duarte JH;Di Meglio P;Hirota K;Ahlfors H;Stockinger B
通讯作者：
Stockinger B
DOI：
10.1084/jem.192.12.1685
发表时间：
2000-12-18
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
den Haan JM;Lehar SM;Bevan MJ
通讯作者：
Bevan MJ
影响因子：
6.4
作者：
Askew, David;Harding, Clifford V.
通讯作者：
Harding, Clifford V.