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27, 2020 /--- -- The nervous system and immune system have long been considered independent entities in the body, but a new study has found direct cell interactions between the two.
researchers from Harvard Medical School, the Broad Institute and the Lagan Institute found that pain neurons around the lymph nodes of mice regulate the activity of these lymph nodes, a key part of the immune system.
study, published recently in the journal Cell, is titled "Lymph nodes are innerved by a unique population of sensory neurons with immunomodulatory potential."
from Cell, 2020, doi:10.1016/j.cell.2020.11.028.
new study reveals the cells that mediate between the nervous system and the immune system.
also paves the way for more research into how the nervous system regulates the immune response.
"Once you start to understand how these systems are formed and how they communicate biologically, it opens up huge opportunities to think about how to properly regulate these interactions as a possible treatment strategy," said Alex Shalek, co-author of the paper and a member of the Broad Institute.
Ulrich von Andrian, professor of immunopathology at Harvard Medical School, is a co-author of the paper.
, a postdoctoral fellow at the Von Andrian Laboratory, is the paper's co-lead author and co-author.
co-first author of the paper is Carly G.K. Ziegler, a graduate student at Shalek Labs.
previous studies that shed light on lymph nodes have suggested a possible link between neurons and lymph nodes.
In the new study, the researchers used a variety of methods, including advanced imaging, retrograde tracing, single-cell RNA sequencing, and photogenetics, to map the connections between neurons, immune cells and other types of cells in the lymph nodes of mice.
they found that a region of the spinal cord called the dorsal root ganglion formed a mesh structure that dominates or connects the entire lymph nodes.
in thousands of sensory cells in the back root nerve nodes, the researchers identified only a few cells in a single lymph node that promote the connection.
Ziegler said, "We found about 20 needles in a haystack that dominate the lymph nodes."
it is really challenging to identify and select specific cell bodies in a different set of neurons.
analyzed the gene expression of these sensory cells by using single-cell RNA sequencing, and the researchers found that these sensory cells were primarily pain neurons.
further analysis found that the genes expressed by these neurons were highly diverse, and that they expressed synth proteins and cell surface molecules that were different from the sense neurons that dominate the skin, suggesting that cell-to-cell communication patterns were different.
to determine whether these pain neurons interacted with the lymph nodes, the researchers induced an artificial immune response in mice and found that the neurons responded by increasing density in the swollen lymph nodes.
suggest that these neurons are able to sense and respond effectively to changes in the lymph nodes.
the researchers also found that this communication goes both ways: the neurons themselves regulate cells in the lymph nodes.
used photogenetics to activate these neurons and observed changes in gene expression in specific cells of the lymph nodes, including endotr skin cells.
findings suggest that these neurons are not mere bystanders.
, "We found that they can actually alter a lot of the local environment of the lymph nodes and seem to affect specific cells and structures in particular," Ziegler said.
" researchers are continuing to learn more about the role of these neurons in the lymph nodes, such as the mechanisms they use to interact with the lymph nodes, whether they mobilize specific parts of the immune system, and what happens if these cell circuits are lacking or dysfunctional.
study also provides scientists with a framework to dissect the connections between other systems in the body.
s starting to figure out how to put toolboxes from multiple areas together," says Shalek, a researcher at the University of New China.
will help us gain new biological insights into how our bodies operate as a single integrated system.
" (Bioon.com) Reference: Siyi Huang et al. Lymph nodes are innervated by a unique population of sensory neurons with immunomodulatory potential. Cell, 2020, doi:10.1016/j.cell.2020.11.028.