Brain control of humoral immune responses amenable to behavioural modulation

Zhang, Xu; Lei, Bo; Yuan, Yuan; Zhang, Li; Hu, Lu; Jin, Sen; Kang, Bilin; Liao, Xuebin; Sun, Wenzhi; Xu, Fuqiang; Zhong, Yi; Hu, Ji; Qi, Hai

doi:10.1038/s41586-020-2235-7

Cited by 218 publications

(175 citation statements)

References 20 publications

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“…Recently, we reported that levels of colony stimulating factor 1 receptor (CSF1R) in the spleen, but not postmortem brain, from patients with depression were significantly lower than those of control groups, and that there was a negative correlation between CSF1R and interacting protein SPI1 in the spleen 57 , suggesting a brain-spleen axis in psychiatric disorders such as depression 26,57,58 . A recent study demonstrated that neurons in the central nucleus of the amygdala and the paraventricular nucleus that express corticosteronereleasing hormone are connected to the splenic nerve, indicating a key role of brain-spleen communication in antibody production 59 . Collectively, it is likely that brain-spleen axis plays a key role in a number of disorders related with immune system.…”

Section: Discussionmentioning

confidence: 99%

A key role of the subdiaphragmatic vagus nerve in the depression-like phenotype and abnormal composition of gut microbiota in mice after lipopolysaccharide administration

et al. 2020

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The vagus nerve plays a role in the cross talk between the brain and gut microbiota, which could be involved in depression. The subdiaphragmatic vagus nerve serves as a major modulatory pathway between the brain and gut microbiota. Here, we investigated the effects of subdiaphragmatic vagotomy (SDV) on the depression-like phenotype and the abnormal composition of gut microbiota in mice after lipopolysaccharide (LPS) administration. LPS caused a depression-like phenotype, inflammation, increase in spleen weight, and downregulation of synaptic proteins in the medial prefrontal cortex (mPFC) in the sham-operated mice. In contrast, LPS did not produce a depression-like phenotype and downregulated synaptic proteins in the mPFC after SDV. The spleen weight and plasma levels of proinflammatory cytokines in the SDV + LPS group were lower than those of the sham + LPS group. Interestingly, there were positive correlations between the plasma levels of pro-inflammatory cytokines and spleen weight, suggesting a relationship between inflammatory events and spleen weight. Furthermore, LPS led to significant alterations in gut microbiota diversity in sham-operated mice, but not SDV-operated mice. In an unweighted UniFrac PCoA, the dots representing the sham + LPS group were located far away from the dots representing the other three groups. Our results suggest that LPS produces a depression-like phenotype, increases spleen weight, triggers inflammation, downregulates synaptic proteins in the mPFC, and leads to abnormal composition of gut microbiota via the subdiaphragmatic vagus nerve. It is likely that the vagus nerve plays a crucial role in the brain-gut-microbiota axis.

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Section: Discussionmentioning

confidence: 99%

A key role of the subdiaphragmatic vagus nerve in the depression-like phenotype and abnormal composition of gut microbiota in mice after lipopolysaccharide administration

et al. 2020

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“…At this neuroimmune junction, the neurotransmitters released by sympathetic nerve endings can stimulate specific receptors on immune cells and affect the function of immune cells. For example, activation of the central amygdala (CeA) and paraventricular nucleus (PVN) corticotropin-releasing-hormone neurons control humoral immune responses in a T-cell-dependent manner by promoting splenic sympathetic output and releasing NE ( 45 ). Moreover, under the stimulation of inflammation, the content of NPY secreted by neurogenic, structural, and immune cells is elevated, regulating immune cell function in a paracrine or autocrine manner ( 46 – 48 ).…”

Section: Npy Directly Regulates Immune Cellsmentioning

confidence: 99%

Neuropeptide Y Is an Immunomodulatory Factor: Direct and Indirect

Chen

Liu

et al. 2020

Front. Immunol.

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Neuropeptide Y (NPY), which is widely distributed in the nervous system, is involved in regulating a variety of biological processes, including food intake, energy metabolism, and emotional expression. However, emerging evidence points to NPY also as a critical transmitter between the nervous system and immune system, as well as a mediator produced and released by immune cells. In vivo and in vitro studies based on gene-editing techniques and specific NPY receptor agonists and antagonists have demonstrated that NPY is responsible for multifarious direct modulations on immune cells by acting on NPY receptors. Moreover, via the central or peripheral nervous system, NPY is closely connected to body temperature regulation, obesity development, glucose metabolism, and emotional expression, which are all immunomodulatory factors for the immune system. In this review, we focus on the direct role of NPY in immune cells and particularly discuss its indirect impact on the immune response.

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“…The structure of the spleen recovered gradually by Day 7. Recently, the brain was demonstrated to shape the humoral immunity via splenic innervation [30]. Elucidation of the functional correlation between brain and spleen must be an important objective.…”

Section: Discussionmentioning

confidence: 99%

Autocrine Activation of Cerebral Microglia by Allograft Inflammatory Factor-1

Fukasawa¹,

Kudo²,

Nishihara³

et al. 2020

Preprint

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Allograft inflammatory factor-1 (AIF-1) is a marker for activated microglia. Unilateral common carotid artery occlusion (UCCAO) was conducted to elucidate mechanisms that regulate AIF-1 expression in C57BL/6 male mice. Immunohistochemical reactivity of microglia against anti-AIF-1 antibody was increased significantly in the brain of this model. The increased AIF-1 production was further confirmed by ELISA using brain homogenate. Real-time PCR demonstrated that the increased AIF-1 production was regulated at the transcriptional level. Serum AIF-1 levels were further examined by ELISA and marked increase was observed on Day 1 of UCCAO. To examine the influence of AIF-1, immunohistochemical staining was performed and revealed that the immunoreactivity against anti-Iba-1 antibody was significantly increased in various organs. Among them, the accumulation of Iba-1+ cells were observed prominently in the spleen. Intraperitoneal injection of minocycline, a potent microglia inhibitor, reduced the number of Iba-1+ cells suggesting microglia activation-dependent accumulation. Based on these results, AIF-1 expression was further examined in the murine microglia cell line MG6. AIF-1 mRNA expression and secretion were up-regulated when the cells were cultured under hypoxic condition. Importantly, stimulation of the cells with recombinant AIF-1 induced the expression of AIF-1 mRNA. These results suggest that increased AIF-1 production by microglia in cerebral ischemia regulate the AIF-1 mRNA expression at least in part by an autocrine manner.

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Brain control of humoral immune responses amenable to behavioural modulation

Cited by 218 publications

References 20 publications

A key role of the subdiaphragmatic vagus nerve in the depression-like phenotype and abnormal composition of gut microbiota in mice after lipopolysaccharide administration

A key role of the subdiaphragmatic vagus nerve in the depression-like phenotype and abnormal composition of gut microbiota in mice after lipopolysaccharide administration

Neuropeptide Y Is an Immunomodulatory Factor: Direct and Indirect

Autocrine Activation of Cerebral Microglia by Allograft Inflammatory Factor-1

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