法国南特大学Aurélie Moreau研究团队发现，人耐药树突状细胞通过乳酸合成调节免疫应答。这一研究成果发表在2019年12月3日出版的国际学术期刊《细胞—代谢》上。

研究报告了自体耐受性树突状细胞（ATDC）代表的基于表型、转录组和代谢分析的单核细胞来源的细胞独特子集。 ATDC的特征在于其抑制T细胞增殖和通过分泌因子扩增Treg。ATDC会产生高水平的乳酸，从而影响T细胞对耐受的应答。实际上，T细胞吸收了ATDC分泌的乳酸，导致其糖酵解减少。在体内，ATDC通过降低T细胞增殖能力来促进循环乳酸水平升高，并延缓移植物排斥宿主的疾病。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。

研究人员表示，细胞疗法是治疗患有自身免疫或炎性疾病或接受移植的患者的有前景的方法。根据临床前研究，他们已经产生了人类ATDC，并在一项针对肾脏移植接受者的首次人体临床试验中对其进行了测试。

附：英文原文

Title: Human Tolerogenic Dendritic Cells Regulate Immune Responses through Lactate Synthesis

Author: Eros Marin, Laurence Bouchet-Delbos, Ophélie Renoult, Cédric Louvet, Véronique Nerriere-Daguin, Amy J. Managh, Amandine Even, Matthieu Giraud, Thien Phong Vu Manh, Audrey Aguesse, Gaelle Bériou, Elise Chiffoleau, Brigitte Alliot-Licht, Xavier Prieur, Mikael Croyal, James A. Hutchinson, Natasa Obermajer, Edward K. Geissler, Bernard Vanhove, Gilles Blancho, Marc Dalod, Régis Josien, Claire Pecqueur, Maria-Cristina Cuturi, Aurélie Moreau

Issue&Volume: 2019/12/03

Abstract: Cell therapy is a promising strategy for treating patients suffering from autoimmuneor inflammatory diseases or receiving a transplant. Based on our preclinical studies,we have generated human autologous tolerogenic dendritic cells (ATDCs), which arebeing 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 onphenotypic, transcriptomic, and metabolic analyses. ATDCs are characterized by theirsuppression of T cell proliferation and their expansion of Tregs through secretedfactors. 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-hostdisease by reducing T cell proliferative capacity. The suppression of T cell immunitythrough lactate production by ATDCs is a novel mechanism that distinguishes ATDCsfrom other cell-based immunotherapies.

DOI: 10.1016/j.cmet.2019.11.011

Source: https://www.cell.com/cell-metabolism/fulltext/S1550-4131(19)30618-7