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With each chew of meals we take, our intestinal immune system should make an enormous resolution. Tasked with defending us from international pathogens, these exquisitely delicate cells by some means distinguish pal from foe—destroying invaders whereas tolerating meals and useful micro organism. How the intestine separates the great from the dangerous has lengthy puzzled scientists.
Now, new analysis identifies particular intestine cell sorts that talk with T cells—prompting them to tolerate, assault, or just ignore—and explains how these opposing responses are triggered. The findings, revealed in Science, give scientists a brand new understanding of how the intestinal immune system retains the intestine in steadiness, and will in the end make clear the basis causes and mechanisms of meals allergy symptoms and intestinal illnesses.
“The big question is, how do we survive eating?” says lead creator Maria C.C. Canesso, a postdoctoral fellow within the laboratories of Daniel Mucida and Gabriel D. Victora. “Why do our bodies normally tolerate food, and what goes wrong when we develop food allergies?”
Intestine selections
The intestinal immune system is difficult equipment. Tolerance to meals begins with antigen presenting cells, or APCs, instructing T cells to face down. This sign provides rise to pTregs, a particular sort of T cell that calms the immune response to meals particles, and kicks off a cascade of exercise involving further immune cells that reinforce the message. However with out realizing which particular APCs run the present, it is tough to tease out the ins and outs of the physique’s eventual tolerance to meals and intolerance to pathogens.
“There are so many types of antigen-presenting cells,” Canesso says. “Pinpointing which ones are doing what is a longstanding technical challenge.”
Antigen-presenting cells (APCs) marked in crimson. Credit score: Rockefeller College
She started exploring this conundrum as a Ph.D. scholar within the Mucida lab, which focuses on how the gut balances protection with tolerance. Throughout her postdoc, Canesso additionally joined the Victora lab, which developed a expertise generally known as LIPSTIC that helps scientists catalogue cell-to-cell interactions, significantly amongst immune cells.
“The technological advances made by the Victora lab allowed us to understand immune cell dynamics that would not have been possible using existing tools,” says Mucida, head of the Laboratory of Mucosal Immunology.
After optimizing LIPSTIC for the duty, Canesso and colleagues succeeded in pinpointing these APCs that promote tolerance—a course of primarily dealt with by two sorts: cDC1s and Rorγt+ APCs. These cells seize dietary antigens from ingested meals and current them to T cells, giving rise to the pTregs that guarantee meals tolerance.
“When we first developed LIPSTIC, we were aiming to specifically measure the interactions between B and T cells that promote antibody responses to vaccines,” says Victora, head of the Laboratory of Lymphocyte Dynamics. “It was to Maria’s credit that she was able to adapt this to settings so different from those it was originally intended for.”
In addition they uncovered how infections of the intestines could cause interference, demonstrating in mice that the parasitic worm Strongyloides venezuelensis shifts the steadiness away from tolerance selling APCs and towards people who promote irritation. Certainly, mice contaminated with this worm throughout a primary publicity to a dietary protein show lowered tolerance in the direction of this protein, and indicators of allergy when challenged.
Lastly, the workforce characterised the molecular alerts underpinning these immune shifts, figuring out key cytokines and pathways that affect how APCs current antigens and modulate immune responses. For instance, the an infection induced a surge in pro-inflammatory cytokines akin to IL-6 and IL-12, which have been proven to nudge APC exercise towards inflammatory outcomes. This inflammatory atmosphere seems to override the immune system’s tolerance mechanisms.
“The worm infection induces this an expansion of non-tolerogenic APCs that help deal with the infection, outnumbering the tolerance-related APCs,” Canesso says.
From meals to meals allergy symptoms
Collectively, the findings illuminate how the immune system maintains meals tolerance and, within the case of parasitic infections, spotlight the particular immune mechanisms that may go awry.
“It’s important to note that our findings do not suggest that worm infections trigger food allergies,” clarifies Mucida, head of the Laboratory of Mucosal Immunology. “They reduce tolerance mechanisms while the immune response focuses on dealing with the worms.”
Whereas these findings aren’t instantly related to meals allergy symptoms, they do lay some groundwork for additional investigation into meals intolerance. “If food allergies are derived from dysregulation on intestinal APCs inducing tolerance and protective responses to infections, perhaps we could one day modulate those APCs specifically to prevent food allergies,” Canesso says.
Subsequent, Canesso plans to shift her focus towards youth, exploring how maternal-neonatal interactions form meals intolerance. “Most allergies develop early in life,” she says. “I want to focus on how breast milk and maternal exposure to dietary antigens may influence a baby’s immune system, potentially shaping their risk of developing food allergies.”
Extra info:
Maria C. C. Canesso et al, Identification of antigen-presenting cell–T cell interactions driving immune responses to meals, Science (2024). DOI: 10.1126/science.ado5088
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Intestinal immune system provides new clues to mechanism behind meals tolerance and allergy symptoms (2025, January 28)
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