As food enters the intestine, it embarks on windy, lengthy journey. For most of the route, its surroundings don't appear to change much. But new research shows that the food-processing canal consists of compartments that pace the immune system's reactions to the food passing through--with less aggressive defenses in the first segments where nutrients are absorbed, and more forceful responses at the end, where pathogens are eliminated.
The findings, published in Nature, provide new insights about how the intestine maximizes nutrient uptake while protecting the body from potentially dangerous invading microbes, two seemingly conflicting functions. The research has potential to improve drugs for gastrointestinal disorders, as well as inform the development of oral vaccines.
"At first glance the intestine appears uniform throughout," says the senior author. "But we've found a sophisticated functional system lurking beneath the surface, organized in segments to allow different immune system functions in different locations."
Researchers uncovered a functional segmentation in mice by examining intestinal structures called gut draining lymph nodes, which orchestrate immune responses. The researchers found that nodes in different part of the intestine had different cell composition, and when they challenged the mice with a pathogen such as Salmonella, they saw different immune responses between segments.
Having immune responses separated by location likely increases the chance that the immune system reacts appropriately to what's passing through, the senior author says. Once most nutrients have been absorbed, the system can focus more aggressively on eliminating pathogens without interfering with food uptake.
According to the senior author, the immunological differences between the gut segments could be exploited for a number of therapeutic purposes, including for treating gastrointestinal disorders. For example, by targeting immune-suppressing drugs to the segment where they'll have the most effect, it might be possible to dampen their side-effects. Additionally, outcomes of surgeries that remove part of the intestine could improve if variations between segments were taken into account.
The spectrum of immune responses along the intestine could also be used to make new and better oral vaccines. Thus far, scientists' efforts to design oral vaccines--attractive to many because of the absence of needles--have been stymied by the difficulty of generating a robust immune response (and unless the immune system mounts a strong enough reaction to the vaccine, it cannot create the molecular "memory" of the pathogen needed to prepare the body against recurring attacks). According to the senior author, the muted immune response at the beginning of the intestine might be part of the reason why oral vaccines tend to be less effective than injections.
"In theory, targeting the distant end of the intestine could be more efficient in inducing the immune response required," the senior author says. "If we harness the right region of the gut, we might see some vaccines work that have previously failed."
https://www.rockefeller.edu/news/25935-new-study-reveals-gut-segments-organized-function-opportunities-better-drug-design/
https://www.nature.com/articles/s41586-019-1125-3
Gut immune system is compartmentalized!
- 1,131 views
- Added
Edited
Latest News
How protein synthesis in de…
By newseditor
Posted 22 Apr
Atlas of mRNA variants in d…
By newseditor
Posted 22 Apr
Mapping microbiome in metas…
By newseditor
Posted 22 Apr
Full-length mRNA packaged i…
By newseditor
Posted 22 Apr
Glucose-sensing mechanism t…
By newseditor
Posted 21 Apr
Other Top Stories
Seizures and memory problems in epilepsy may have a common cause
Read more
A transcription factor involved in pulmonary fibrosis identified
Read more
Tau in malfunctioning brain cells of Alzheimer's!
Read more
Why neurons consume so much fuel even when at rest
Read more
Motivation circuit in the mouse brain
Read more
Protocols
A programmable targeted pro…
By newseditor
Posted 23 Apr
MemPrep, a new technology f…
By newseditor
Posted 08 Apr
A tangible method to assess…
By newseditor
Posted 08 Apr
Stem cell-derived vessels-o…
By newseditor
Posted 06 Apr
Single-cell biclustering fo…
By newseditor
Posted 01 Apr
Publications
Neuronal activity rapidly r…
By newseditor
Posted 22 Apr
A perspective on muscle phe…
By newseditor
Posted 22 Apr
Foxp1 suppresses cortical a…
By newseditor
Posted 22 Apr
Single-cell long-read seque…
By newseditor
Posted 22 Apr
Unlocking potential: the ro…
By newseditor
Posted 22 Apr
Presentations
Hydrogels in Drug Delivery
By newseditor
Posted 12 Apr
Lipids
By newseditor
Posted 31 Dec
Cell biology of carbohydrat…
By newseditor
Posted 29 Nov
RNA interference (RNAi)
By newseditor
Posted 23 Oct
RNA structure and functions
By newseditor
Posted 19 Oct
Posters
A chemical biology/modular…
By newseditor
Posted 22 Aug
Single-molecule covalent ma…
By newseditor
Posted 04 Jul
ASCO-2020-HEALTH SERVICES R…
By newseditor
Posted 23 Mar
ASCO-2020-HEAD AND NECK CANCER
By newseditor
Posted 23 Mar
ASCO-2020-GENITOURINARY CAN…
By newseditor
Posted 23 Mar