The appendix has long had a reputation as a redundant organ with no real function. You might want to hang on to it if you can, however.
Doctors often remove it even in mild cases of appendicitis to prevent future infection and rupture, which may not always be necessary. New research on the way innate lymphoid cells (ILCs) protect against infection in people with compromised immune systems may redeem this misunderstood organ.
“Our study was to investigate the ILCs in the gut [of mice] and how they might contribute to the function and protection of the gut,” says Gabrielle Belz, of Melbourne’s Walter and Eliza Hall Institute of Medical Research. “At the same time, we were interested to know how different immune cells impacted the different parts of the gut.”
ILCs can be found “underlying all the body’s surfaces, including the skin, the lungs, the gut, and the reproductive tract, and play a very important and broad role in protecting the body from infections and responses to environmental insults,” says Belz.
Belz’s team worked in collaboration with a team headed by Eric Vivier at the Centre d’Immunologie de Marseille-Luminy, France. Together, they set out to explore how ILC3s (one group of ILCs) function during and after a gut infection – particularly how they altered immune protection.
The study, published in Nature Immunology, found that in mice, gut infections begin in the cecum, a small pouch that is considered to be the beginning of the large intestine, and which contains a large patch of ILC3s near its tip. The team infected mice with the murine pathogen Citrobacter rodentium, which establishes first in the cecum. Then they removed the ILC3s, which caused shrinkage of the cecum and inflammation in the colon. Moreover, they uncovered a “layered contribution” of each of the different types of immune cells in the cecum.
“Thus, surprisingly, altering the balance of immune cells significantly affected what was happening in the cecum, suggesting that a similar effect might occur in humans in the appendix,” Belz says. “This highlights that simply disposing of this organ may not always be in our best interests.”
While the appendix is not required for digestive functions in humans, Belz says, “It does house symbiotic bacteria proposed by Randal Bollinger and Bill Parker at Duke University to be important for overall gut health, but particularly when we get a gut infection resulting in diarrhoea.”
Infections of this kind clear the gut not only of fluids and nutrients but also good bacteria. Their research suggests that those ILCs housed in the appendix may be there as a reserve to repopulate the gut with good bacteria after a gut infection.
ILCs are hardier than other immune cells, and thus vital to fighting bacterial infections in people with compromised immune systems, such as those in cancer treatment; they are some of the few immune cells that can survive chemotherapy.
Belz says that changing the way the appendix is regarded (from vestigial to integral) may also help prevent unnecessary appendix operations. In non-emergency cases of appendicitis, for instance, non-surgical treatments such as antibiotics “can be used to endeavor to calm the inflammation down in the cecum and appendix,” she says. And a healthy appendix may be helping to keep your gut microbiome balanced. Belz has conducted prior research that shows that diet, particularly leafy green and cruciferous vegetables, may help produce ILCs as well.
More study can also help understand how ILCs play a role in allergic diseases such as asthma, inflammatory bowel disease, and psoriasis. At the very least, Belz says, “It seems likely that [the appendix] is an integral part of the immune system.”
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