Experimental Immunology Branch, National Cancer Institute, NIH, Bethesda, MD, USA.
Synapse and Neural Circuit Research Section, National Institute of Neurological Disorders and Stroke, NIH, Bethesda, MD, USA.
Immunity. 2023 Jul 11;56(7):1533-1547.e7. doi: 10.1016/j.immuni.2023.06.001. Epub 2023 Jun 23.
The crosstalk between the immune and neuroendocrine systems is critical for intestinal homeostasis and gut-brain communications. However, it remains unclear how immune cells participate in gut sensation of hormones and neurotransmitters release in response to environmental cues, such as self-lipids and microbial lipids. We show here that lipid-mediated engagement of invariant natural killer T (iNKT) cells with enterochromaffin (EC) cells, a subset of intestinal epithelial cells, promoted peripheral serotonin (5-HT) release via a CD1d-dependent manner, regulating gut motility and hemostasis. We also demonstrated that inhibitory sphingolipids from symbiotic microbe Bacteroides fragilis represses 5-HT release. Mechanistically, CD1d ligation on EC cells transduced a signal and restrained potassium conductance through activation of protein tyrosine kinase Pyk2, leading to calcium influx and 5-HT secretion. Together, our data reveal that by engaging with iNKT cells, gut chemosensory cells selectively perceive lipid antigens via CD1d to control 5-HT release, modulating intestinal and systemic homeostasis.
免疫和神经内分泌系统之间的串扰对于肠道内稳态和肠脑通讯至关重要。然而，目前尚不清楚免疫细胞如何参与肠道对激素和神经递质释放的感知，以响应环境线索，如自身脂质和微生物脂质。我们在这里表明，脂质介导的固有自然杀伤 T(iNKT)细胞与肠嗜铬细胞（EC）细胞的相互作用，EC 细胞是肠道上皮细胞的一个子集，通过 CD1d 依赖性方式促进外周 5-羟色胺（5-HT）释放，调节肠道蠕动和止血。我们还证明了共生微生物脆弱拟杆菌的抑制性鞘脂通过抑制 5-HT 释放。在机制上，EC 细胞上的 CD1d 交联通过激活蛋白酪氨酸激酶 Pyk2 转导信号并抑制钾电导，导致钙内流和 5-HT 分泌。总之，我们的数据表明，通过与 iNKT 细胞相互作用，肠道化学感觉细胞通过 CD1d 选择性感知脂质抗原，以控制 5-HT 释放，调节肠道和全身内稳态。
