As a self-certified NOT immunology OR neuroscience girly, I was a bit intimidated when I had to read a paper on interorgan neuroimmune circuits for my Advanced Immunology Course (because yes, although immunology scares me, I am, in fact, back for more). However, I found this paper (“An interorgan neuroimmune circuit promotes visceral hypersensativity” https://doi.org/10.21203/rs.3.rs-6221928/v1) to be super cool, so I am sharing it with you all here on Substack!
The TL;DR
This paper mainly focused on a pain disorder called interstitial cystitis/bladder pain syndrome (IC/BPS). Patients who have this disorder often also experience irritable bowel syndrome (IBS). The group that authored this paper found that this was due to a mast cell-sensory neuron circuit that both initiates inflammation in the bladder and then propagates this sensitivity to the colon.
Let’s break this down
Cross-talk between the bladder and colon
Both of these organs are mainly responsible for removing waste from our bodies, which requires them to sense a variety of immunological and mechanical cues and respond to them. When these conditions change, in the case of inflammation in the bladder for IC/BPS patients, pain occurs. Many of these patients also experience pain and discomfort in the colon, as IBP is comorbid in up to 75% of patients with IC/BPS.
This study found that there is a set of shared neurons between these two organs. Not only that, but upon stimulating infection in the bladder, there was also inflammation in the colon. This may explain why other pathologies drive multiorgan visceral pain syndromes, as well as why visceral pain is so difficult to localize.
Mast Cells
Mast cells are a subset of immune cells that mainly localize to barrier surfaces that are exposed to internal and external pathogens, such as the skin, GI tract, and respiratory system. The antibody IgE (the antibody responsible for allergic reactions) acts on these cells and leads to symptoms such as itching. This paper showed that Mast cells, specifically those expressing the protein MRGPRX2, interact with interorgan neurons to propagate pain from the bladder to the colon.
Think of it like one of those DIY phones that are really two cups connected by a string: the mast cells transmit the signal/ pain from the bladder to the colon, or the cups, via interorgan neurons, which act like the string.
So, why do we care about this?
Historically, cross-talk between organs has been attributed to the circulation of hormones or other immune factors through our blood. This paper adds to the idea that organs communicate humoraly by establishing that there can be a physical connection (via neurons) as well. This observation provides an alternative way to treat these pain disorders, as there is potential to target the subset of mast cells that was described above.
This was an extremely crude summary of the paper- if you are interested in diving deeper, check out the paper here! Feel free to leave a comment with your thoughts below!
Hi, I’m Isabella!
I’m a Ph.D. student passionate about science communication and mentoring younger scientists. I post on My Ph.Diary. on Sundays, Wednesdays, and Fridays, sharing my lab experiences, advice on navigating research, and any biological topics that pique my curiosity. Subscribe below to stay updated!
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What is the alternative way to treat these pain disorders?
Ugh immunology is my true love. It’s so complex but so so so elegant. Excellent work :)