Stearoyl‐CoA desaturases (SCD) are endoplasmic reticulum (ER)‐associated enzymes that catalyze the synthesis of the monounsaturated fatty acids (MUFAs). As such, SCD play important roles in maintaining the intracellular balance between saturated fatty acid (SFAs) and MUFAs. The roles of SCD in CD4⁺ T‐helper cell responses are currently unexplored. Here, we have found that murine and human follicular helper T (T_FH) cells express higher levels of SCD compared to non‐T_FH cells. Further, the expression of SCD in T_FH cells is dependent on the T_FH lineage‐specification transcription factor BCL6. We found that the inhibition of SCD impaired T_FH cell maintenance and shifted the balance between T_FH and follicular regulatory T (T_FR) cells in the spleen. Consequently, SCD inhibition dampened germinal center B‐cell responses following influenza immunization. Mechanistically, we found that SCD inhibition led to increased ER stress and enhanced T_FH cell apoptosis in vitro and in vivo. These results reveal a possible link between fatty acid metabolism and cellular and humoral responses induced by immunization or potentially, autoimmunity.

中文翻译：

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硬脂酰辅酶A去饱和酶的抑制抑制滤泡辅助T细胞和生发中心B细胞反应。

硬脂酰辅酶 A 去饱和酶 (SCD) 是内质网 (ER) 相关酶，可催化单不饱和脂肪酸 (MUFA) 的合成。因此，SCD 在维持饱和脂肪酸 (SFA) 和 MUFA 之间的细胞内平衡方面发挥着重要作用。目前尚未探索SCD 在 CD4 ⁺ T 辅助细胞反应中的作用。在这里，我们发现与非 T _FH细胞相比，鼠和人滤泡辅助性 T (T _FH ) 细胞表达更高水平的 SCD 。此外，T _FH细胞中 SCD 的表达取决于 T _FH谱系特异性转录因子 BCL6。我们发现抑制 SCD 会损害 T _FH细胞维持并改变脾脏中T _FH和滤泡调节性 T (T _FR ) 细胞之间的平衡。因此，SCD 抑制抑制了流感免疫后的生发中心 B 细胞反应。从机制上讲，我们发现 SCD 抑制导致 ER 应激增加和体外和体内T _FH细胞凋亡增强。这些结果揭示了脂肪酸代谢与免疫或潜在的自身免疫诱导的细胞和体液反应之间可能存在联系。