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Brain pathway capable of controlling adaptive immunity discovered.

a study from researchers led by Tsinghua University identifies a specific brain-spleen neural connection capable of regulating the formation of plasma cells autonomously of an immune response. The team states this neurally controlled immune modulation can be triggered by a behavioral regimen.

Plasma cells are a type of immune cell originating in the bone marrow as B cells, another type of white blood cell. Once the B cells leave the bone marrow and encounter a foreign antigen they differentiate into plasma cells to secrete a large number of specific antibodies depending on the pathogen encountered.

As an inflammatory response may also be present due to a foreign invader attack, cytokines, a product of this inflammation can also play a part in the maturation of plasma cells and the type of antibody they produce. To-date this immune response is the only established mechanism to produce and regulate this adaptive immune response.

Brain regulation of immunity

Now, a study from researchers led by Tsinghua University identifies a specific brain-spleen neural connection capable of regulating the formation of plasma cells autonomously of an immune response. The team states this neurally controlled immune modulation can be triggered by a behavioral regimen. The study is published in the journal Nature.

Previous studies have indicated pathways linking the brain to the immune system are normally activated by signals from the immune system, to regulate immunity. These pathways are thought to be initiated by immune cells and proinflammatory cytokines.

The concept involving the brain modulating the immune system stems from the theory of stress-producing an immune response independently of an immune attack, with much work done to identify autonomous communication pathways between the two systems.

It has been hypothesized these independent neuroimmune pathways may stem from the lymphoid organs known to be innervated by branches of the autonomic nervous system, although this has never been proven. The current study identifies a stress-controlled brain-spleen connection modulating the formation of plasma cells autonomously, activated by behavioral training.

Stress-linked immunity

The current study tracks the independent pathway of communication between the brain and the immune system in mice via the injection of the pseudorabies virus into their spleens, a major lymphoid organ.

Results show the central nucleus of the amygdala (CeA) and the paraventricular nucleus (PVN), two prominent brain regions in stress, contain neurons expressing corticotropin-releasing hormone (CRH) connected to the splenic nerve. Data findings show the ablation of these CRH neurons reduces plasma cell formation, with pharmacogenetic activation of the same neurons increasing plasma cell production.

The lab states they then developed a behavioral regimen involving mice standing on an elevated platform, an action to cause them stress, which in turn activates PVN and CeA neurons to increase plasma cell formation.

They go on to add mice ‘immunized’ using this stress training produced more Immunoglobulin G (IgG) antibody, the most common antibodies in humans, whose formation is dependent on CRH neurons in the PVN and CeA. They conclude their work reveals neuronal regulation of adaptive immunity suggesting the possibility of boosting the immune system through behavioral training.

Lower stress to control immunity

The team surmises they have identified a stress-based brain–spleen pathway autonomously regulating adaptive immune responses. For the future, the researchers state the ability of the brain to regulate adaptive immunity hints at the possibility of enhancing the host’s immune system via stress training.

Source: ShanghaiTech University

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