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Human Tolerogenic Dendritic Cells Regulate Immune Responses through Lactate Synthesis.
Cell Metabolism ( IF 27.7 ) Pub Date : 2019-12-03 , DOI: 10.1016/j.cmet.2019.11.011 Eros Marin 1 , Laurence Bouchet-Delbos 1 , Ophélie Renoult 2 , Cédric Louvet 1 , Véronique Nerriere-Daguin 3 , Amy J Managh 4 , Amandine Even 1 , Matthieu Giraud 1 , Thien Phong Vu Manh 5 , Audrey Aguesse 6 , Gaelle Bériou 1 , Elise Chiffoleau 1 , Brigitte Alliot-Licht 7 , Xavier Prieur 8 , Mikael Croyal 6 , James A Hutchinson 9 , Natasa Obermajer 10 , Edward K Geissler 9 , Bernard Vanhove 3 , Gilles Blancho 1 , Marc Dalod 5 , Régis Josien 11 , Claire Pecqueur 12 , Maria-Cristina Cuturi 3 , Aurélie Moreau 3
Cell Metabolism ( IF 27.7 ) Pub Date : 2019-12-03 , DOI: 10.1016/j.cmet.2019.11.011 Eros Marin 1 , Laurence Bouchet-Delbos 1 , Ophélie Renoult 2 , Cédric Louvet 1 , Véronique Nerriere-Daguin 3 , Amy J Managh 4 , Amandine Even 1 , Matthieu Giraud 1 , Thien Phong Vu Manh 5 , Audrey Aguesse 6 , Gaelle Bériou 1 , Elise Chiffoleau 1 , Brigitte Alliot-Licht 7 , Xavier Prieur 8 , Mikael Croyal 6 , James A Hutchinson 9 , Natasa Obermajer 10 , Edward K Geissler 9 , Bernard Vanhove 3 , Gilles Blancho 1 , Marc Dalod 5 , Régis Josien 11 , Claire Pecqueur 12 , Maria-Cristina Cuturi 3 , Aurélie Moreau 3
Affiliation
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Cell therapy is a promising strategy for treating patients suffering from autoimmune or inflammatory diseases or receiving a transplant. Based on our preclinical studies, we have generated human autologous tolerogenic dendritic cells (ATDCs), which are being tested in a first-in-man clinical trial in kidney transplant recipients. Here, we report that ATDCs represent a unique subset of monocyte-derived cells based on phenotypic, transcriptomic, and metabolic analyses. ATDCs are characterized by their suppression of T cell proliferation and their expansion of Tregs through secreted factors. ATDCs produce high levels of lactate that shape T cell responses toward tolerance. Indeed, T cells take up ATDC-secreted lactate, leading to a decrease of their glycolysis. In vivo, ATDCs promote elevated levels of circulating lactate and delay graft-versus-host disease by reducing T cell proliferative capacity. The suppression of T cell immunity through lactate production by ATDCs is a novel mechanism that distinguishes ATDCs from other cell-based immunotherapies.
中文翻译：
人类耐受性树突状细胞通过乳酸合成调节免疫反应。
细胞疗法是治疗患有自身免疫性或炎性疾病或接受移植的患者的有前途的策略。根据我们的临床前研究，我们已经生成了人类自体耐受性树突状细胞（ATDC），并在一项针对肾脏移植受者的首次人体临床试验中对其进行了测试。在这里，我们报告ATDCs代表基于表型，转录组和代谢分析的单核细胞衍生细胞的独特子集。ATDC的特征在于其抑制T细胞增殖和通过分泌因子扩展Treg。ATDC会产生高水平的乳酸，从而影响T细胞对耐受的反应。实际上，T细胞吸收了ATDC分泌的乳酸，导致其糖酵解减少。体内，ATDC通过降低T细胞的增殖能力来促进循环血乳酸水平升高并延缓移植物抗宿主病。通过ATDC产生乳酸来抑制T细胞免疫是一种将ATDC与其他基于细胞的免疫疗法区分开的新机制。
更新日期：2019-12-04
中文翻译：
人类耐受性树突状细胞通过乳酸合成调节免疫反应。
细胞疗法是治疗患有自身免疫性或炎性疾病或接受移植的患者的有前途的策略。根据我们的临床前研究，我们已经生成了人类自体耐受性树突状细胞（ATDC），并在一项针对肾脏移植受者的首次人体临床试验中对其进行了测试。在这里，我们报告ATDCs代表基于表型，转录组和代谢分析的单核细胞衍生细胞的独特子集。ATDC的特征在于其抑制T细胞增殖和通过分泌因子扩展Treg。ATDC会产生高水平的乳酸，从而影响T细胞对耐受的反应。实际上，T细胞吸收了ATDC分泌的乳酸，导致其糖酵解减少。体内，ATDC通过降低T细胞的增殖能力来促进循环血乳酸水平升高并延缓移植物抗宿主病。通过ATDC产生乳酸来抑制T细胞免疫是一种将ATDC与其他基于细胞的免疫疗法区分开的新机制。
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