比利时哈塞尔特大学Markus Kleinewietfeld团队近期取得重要工作进展，他们研究发现钠干扰线粒体呼吸并诱导功能失调的Treg。相关研究成果2023年2月7日在线发表于《细胞—代谢》杂志上。

据介绍，FOXP3⁺调节性T细胞（Treg）是外周耐受的核心，其失活与自身免疫相关。功能异常的自身免疫Treg表现出促炎性特征和线粒体代谢改变，但其影响因素仍不清楚。高盐（HS）已被证实可改变免疫功能并促进自身免疫。

通过研究人类Treg的纵向转录变化，研究人员发现HS诱导代谢重编程，再现了自身免疫Treg的特征。从机理上讲，细胞外HS通过干扰电子运输链（ETC）来提高细胞内Na⁺，干扰线粒体呼吸。临时HS遭遇或复合III阻断引起的代谢紊乱会迅速诱导促炎信号和FOXP3下调，导致体内外长期功能障碍。通过抑制线粒体Na⁺/Ca2⁺交换剂（NCLX）可以逆转HS诱导的效应。

总之，这一结果表明，盐可能有助于代谢重编程，短期HS会干扰人体Treg的代谢适应性和长期功能，对自身免疫具有重要意义。

附：英文原文

Title: Sodium perturbs mitochondrial respiration and induces dysfunctional Tregs

Author: Beatriz F. Crte-Real, Ibrahim Hamad, Rebeca Arroyo Hornero, Sabrina Geisberger, Joris Roels, Lauren Van Zeebroeck, Aleksandra Dyczko, Marike W. van Gisbergen, Henry Kurniawan, Allon Wagner, Nir Yosef, Susanne N.Y. Weiss, Klaus G. Schmetterer, Agnes Schrder, Luka Krampert, Stefanie Haase, Hendrik Bartolomaeus, Niels Hellings, Yvan Saeys, Ludwig J. Dubois, Dirk Brenner, Stefan Kempa, David A. Hafler, Johannes Stegbauer, Ralf A. Linker, Jonathan Jantsch, Dominik N. Müller, Markus Kleinewietfeld

Issue&Volume: 2023/02/07

Abstract: FOXP3+ regulatory T cells (Tregs) are central for peripheral tolerance, and their deregulation is associated with autoimmunity. Dysfunctional autoimmune Tregs display pro-inflammatory features and altered mitochondrial metabolism, but contributing factors remain elusive. High salt (HS) has been identified to alter immune function and to promote autoimmunity. By investigating longitudinal transcriptional changes of human Tregs, we identified that HS induces metabolic reprogramming, recapitulating features of autoimmune Tregs. Mechanistically, extracellular HS raises intracellular Na+, perturbing mitochondrial respiration by interfering with the electron transport chain (ETC). Metabolic disturbance by a temporary HS encounter or complex III blockade rapidly induces a pro-inflammatory signature and FOXP3 downregulation, leading to long-term dysfunction in vitro and in vivo. The HS-induced effect could be reversed by inhibition of mitochondrial Na+/Ca2+ exchanger (NCLX). Our results indicate that salt could contribute to metabolic reprogramming and that short-term HS encounter perturb metabolic fitness and long-term function of human Tregs with important implications for autoimmunity.

DOI: 10.1016/j.cmet.2023.01.009

Source: https://www.cell.com/cell-metabolism/fulltext/S1550-4131(23)00009-8