Inhibition of glucose metabolism selectively targets autoreactive follicular helper T cells.
Inhibition of glucose metabolism selectively targets autoreactive follicular helper T cells.
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DOI：
10.1038/s41467-018-06686-0
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发表时间：
2018-10-22
影响因子：
16.6
通讯作者：
Morel L
中科院分区：
文献类型：
--
作者：
Choi SC;Titov AA;Abboud G;Seay HR;Brusko TM;Roopenian DC;Salek-Ardakani S;Morel L
滤泡辅助性T（TFH）细胞在系统性红斑狼疮中扩增，需要它们产生高亲和力自身抗体。然而，消除TFH细胞将损害针对病毒和细菌病原体的保护性抗体的产生。在这里，我们表明，抑制葡萄糖代谢的结果在一个急剧减少的频率和数量的TFH细胞在狼疮易感小鼠。然而，这种抑制作用对用外源性抗原免疫后T细胞依赖性抗体的产生或对由流感感染诱导的病毒特异性TFH细胞的频率几乎没有影响。相反，去甲氨醇分解抑制减少免疫诱导的和自身免疫性TFH细胞和体液应答。溶质转运蛋白基因特征表明自身免疫TFH细胞和外源性抗原特异性TFH细胞之间的葡萄糖和氨基酸通量不同。因此，阻断葡萄糖代谢可以提供一种有效的治疗方法，通过消除自身反应性TFH细胞，同时保持对病原体的保护性免疫来治疗全身性自身免疫。T细胞功能依赖于不同的代谢通量。在这里，作者显示了对自身抗原和微生物抗原的体液应答的不同代谢要求：虽然葡萄糖对于抗病毒Tfh和抗体应答是必需的，但必须建立针对自身抗原的这些应答。
Follicular helper T (TFH) cells are expanded in systemic lupus erythematosus, where they are required to produce high affinity autoantibodies. Eliminating TFH cells would, however compromise the production of protective antibodies against viral and bacterial pathogens. Here we show that inhibiting glucose metabolism results in a drastic reduction of the frequency and number of TFH cells in lupus-prone mice. However, this inhibition has little effect on the production of T-cell-dependent antibodies following immunization with an exogenous antigen or on the frequency of virus-specific TFH cells induced by infection with influenza. In contrast, glutaminolysis inhibition reduces both immunization-induced and autoimmune TFH cells and humoral responses. Solute transporter gene signature suggests different glucose and amino acid fluxes between autoimmune TFH cells and exogenous antigen-specific TFH cells. Thus, blocking glucose metabolism may provide an effective therapeutic approach to treat systemic autoimmunity by eliminating autoreactive TFH cells while preserving protective immunity against pathogens. T cell functions depend on distinct metabolic fluxes. Here the authors show different metabolic requirements of humoral responses to self versus microbial antigens: while glucose is dispensable for antiviral Tfh and antibody responses, it is essential to mount these responses against autoantigens.
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影响因子：
7.3
作者：
Kim SJ;Lee K;Diamond B
通讯作者：
Diamond B
影响因子：
64.5
作者：
Buck MD;Sowell RT;Kaech SM;Pearce EL
通讯作者：
Pearce EL
DOI：
10.1084/jem.20151722
发表时间：
2016-05-02
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Domeier PP;Chodisetti SB;Soni C;Schell SL;Elias MJ;Wong EB;Cooper TK;Kitamura D;Rahman ZS
通讯作者：
Rahman ZS
DOI：
10.1073/pnas.0807309106
发表时间：
2009-02-03
影响因子：
11.1
作者：
Bubier, Jason A.;Sproule, Thomas J.;Roopenian, Derry C.
通讯作者：
Roopenian, Derry C.
影响因子：
4
作者：
Cantor, Joseph M.;Ginsberg, Mark H.
通讯作者：
Ginsberg, Mark H.