Scientists from ShanghaiTech and Tsinghua Universities Discover a Novel Neuroimmune Pathway

ON2020-04-30TAG: ShanghaiTech UniversityCATEGORY: Features

On 29 April 2020, a research work carried out collaboratively by Professors Qi Hai and Zhong Yi from Tsinghua University and Professor Hu Ji from the School of Life Science and Technology (SLST) of ShanghaiTech University was published in Nature entitled “Brain control of humoral immune responses amenable to behavioural modulation”. The researchers identify a specific brain-spleen neural connection which can autonomically regulate the formation of plasma cells. This study, for the first time, shows that immune modulation can be achieved through a bodily behavioural regimen.

In order to study the brain origin of autonomic neutral activities regulating humoral immunity, the researchers applied retrograde tracking by injection of pseudorabies virus into the spleen and define the PVN and the CeA as two prominent brain stress regions neurally connected to the spleen. Cell ablation or pharmacogenetic inhibition of CRH neurons in both PVN and CeA reduced plasma cell formation, whereas pharmacogenetic activation of these neurons elevated plasma cell abundance following immunisation. 

They further developed a behavioural regimen that allows mice to stand on an elevated platform (EPS) to activate PVN and CeA CRH neurons and increase plasma cell formation following immunisation. Importantly, mice immunised with EPS behavioural regimen produce more antigen-specific IgG antibodies in a manner dependent on CRH neurons in the PVN and CeA. This study not only identifies a specific brain-spleen neural connection that modulates the formation of plasma cell formation autonomically, but also demonstrates immune modulation by a bodily behavioural regimen. Therefore, this work reveals neuronal regulation of adaptive immunity and suggests the possibility to enhance host immune capacity through behavioural intervention.

Yuan Yuan, a PhD student from SLST of ShanghaiTech, is a co-first author of the paper, and Professor Hu Ji serves as a co-corresponding author.

Stress refers to the state of high tension in animals or humans caused by external stimulation. In modern society where competition is fierce, people are under stress every day, and pandemics like COVID-19 are an additional strong source of stress. Therefore, the field of stress neurobiology is at the forefront of science and is in high demand worldwide. Professor Hu's team has been working on neural circuits and cellular mechanisms of stress and a number of important articles have been published in scientific journals such as Current Biology and Neuron.

Optogenetic stimulation and electrophysiological records confirm that splenic nerve activity responds to central stimulation

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Professor Hu Ji, associate professor at School of Life Science and Technology, ShanghaiTech University

Prof. Hu’s main research directions are: 1. Neural mechanism of stress; 2. Circuit mechanism of neuropsychopharmacology; 3. New strategies for the treatment of neurological and psychiatric diseases. Some important achievements were published as first author or corresponding author in top journals like ScienceNatureNeuronCurrent Biology, etc. At present, his research group has 8 graduate students, 2 assistant researchers and 1 technician; the average age of the research team is 30 years old.

“Prof. Hu is a very active thinking person who is very keen on capturing scientific problems. Under his guidance, we can always find the way to finishline when working on research subjects. The four years in Prof. Hu's lab were the four years when I gradually became familiar with scientific research and loved scientific research. I am very fortunate to meet Prof. Hu, and I am very grateful to have opportunity spending a very memorable years in Prof. Hu’s lab. I have benefited a lot!” -Feelings from Yuan Yuan.

Yuan Yuan, Class of 2020 PhD student of SLST

“The co-first author of this paper, Yuan Yuan, is my first graduate student at ShanghaiTech. Starting this project in 2015 with Tsinghua University is a large-span cooperation in the fields of nerves and immunity. Carrying out new research work and exploring areas that the laboratory has never been exposed to are all great challenges for me and Yuan Yuan. We try to be the one who builds a new system and framework. During this process, although she took a lot of detours, she finally reached the finish line and learned a lot of skills.” -Prof. Hu Ji’s evaluation to Yuan Yuan. 

Group photo of Hu's team taken in 2019