Department of Pathology, Immunology, and Laboratory Medicine, University of Florida, 1395 Center Drive, Gainesville, FL, 32610, USA.
The Jackson Laboratory, 600 Main Street, Bar Harbor, ME, 04609, USA.
Nat Commun. 2018 Oct 22;9(1):4369. doi: 10.1038/s41467-018-06686-0.
Follicular helper T (T) cells are expanded in systemic lupus erythematosus, where they are required to produce high affinity autoantibodies. Eliminating T 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 T 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 T cells induced by infection with influenza. In contrast, glutaminolysis inhibition reduces both immunization-induced and autoimmune T cells and humoral responses. Solute transporter gene signature suggests different glucose and amino acid fluxes between autoimmune T cells and exogenous antigen-specific T cells. Thus, blocking glucose metabolism may provide an effective therapeutic approach to treat systemic autoimmunity by eliminating autoreactive T cells while preserving protective immunity against pathogens.
滤泡辅助 T（T）细胞在系统性红斑狼疮中扩增，在那里它们需要产生高亲和力的自身抗体。然而，消除 T 细胞会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会导致狼疮易感小鼠中 T 细胞的频率和数量急剧减少。然而，这种抑制对用外源性抗原免疫接种后 T 细胞依赖性抗体的产生或流感感染诱导的病毒特异性 T 细胞的频率几乎没有影响。相比之下，谷氨酰胺分解抑制减少了免疫诱导和自身免疫 T 细胞和体液反应。溶质转运体基因特征表明自身免疫 T 细胞和外源性抗原特异性 T 细胞之间存在不同的葡萄糖和氨基酸通量。因此，阻断葡萄糖代谢可能通过消除自身反应性 T 细胞而保留针对病原体的保护性免疫来提供治疗系统性自身免疫的有效方法。
