Intestinal Imamune System Gives New Clues to Mechanism Behind Food tolerance and Allergies

With Every Bite of Food We Take, Ouro Intestinal Imamune System Must Make a Big Decision. Tasked with Defending US from Foreign Pathogens, these Exquisitely Sensitive Cells Somehow Distinguish Frly from Foe – Destrogying invaders while toleratting food and helpful bacteria. How the gut separate the good from the bad has long puzzled scientists.

Now, New Research Identifies Specific Gut Cell Types That Communicate with T Cells – Prompting Them Tolerate, Attack, Or Simply Ignore – Aame Explains How these Opposing Responses Are Triggered. The Findings, published in ScienceGive Scientists a New Understanding of How the Intestinal Imamune System Keps the Gut In Balance, and May Ultimately Shed Light on the Root Causes and Mechanisms of Food Allergies and intestinal dissees.

“The Big Questions is, How of We Survive Eating?” SAYS LEAD AUTHOR MARIA CC CANESSO, Postdoctoral Fellow in the Laboratories of Daniel Mucida and Gabriel D. Victora. “Why from Our Bodies Normally Tolerate Food, and What Goes Wrong when We Develop Food Allergies?”

GUT DECISIONS

The intestinal imamune system is complicated machine. Tolerance to food begins with antigen Presenting Cells, or APCs, Instruct T Cells to Stand Down. This signs Gives Rise to Ptregs, Special Type of T Cell That Calms The Imamune Response to Food Particles, and Kicks Off a Cascade of Activity Eviving AddiTeal Imamune Cells That Reinforce The Message. But Without Knowing Which Specific Apcs Run the Show, It’s Difficult to Tease Out the Ins and Outs of the Body’s Eventual Tolerance to Food and Intolerance to Pathogens.

“There Are So Many Types of Antigen-Presenting Cells,” Canesto says. “Pinpointing Which One Are Doing What is a Longstanding Technical Challenge.”

She began exploiting this conundum as a Ph.D. Student in the Mucida Lab, Which focuses on How the Intestine Balances Defense with Tolerance. DURING HER POSTDOC, CANSSO ALSO JOINED THE VICTOR LAB, WHICH DEVELOPED A TECHNOLOGY KNOWN AS LIPSTIC THAT HELPS SCIENTISTS CATALOGUE CELL-TO-CELL INTERACTIONS, PARTICULALY AMONG IMMEMBER CELLS.

“The Technological Advances Made by the Victor Lab Allowed Us to Underser Imamune 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 task, canness and colleges succceed in pinpointing those plas that promote tolerance – the process primarily handled by two types: cdc1s and rorγt+ APCs. These Cells Capture Dietary Antigen from Ingredized Food and Present Them To T Cells, Giving Rise to the Ptregs That Ensure Food 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 Victor, 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 Thhose It Was Originally Intended for.”

They also uncovered How infections of the intestines can cause interference, demonstrating in mice that the parasitic worm strongyloides venezuelensis shifts the balance away from tolerance promoting apcs and toward thhose that promote infamination. INDEED, MICE INFECTED WITH THIS WORM DURING A FIRST EXPOSURE TO DIETARY PROTEIN DISPLAY REDUCED TOLERANCES THIS PROTEIN, AND SIGNS OF ALLERGY WHEN CHALLENGED.

Finally, The Team Characterized the Molecular Signals Underpinning These Imamune Shifts, Identifying Key Cytokines and Pathways That Influence How Apcs Present Antigen and Modulate Imamune Responses. Example, the infection Induced a emerge in pro-inflammory cytokines such as IL-6 and IL-12, Which have benwn to nude APC Activity Toward Inflammatory Outcomes. This infmmatory Environment Appears to Override the Imamune System’s Tolerance Mechanisms.

“The Worm Infection Induces this an expansion of non-tolerogenic Apcs That Help Deal With the Infection, Outnumbering the Tolerance-Relanted APCs,” Canesto says.

From food to food allergies

Together, The Findings Illuminate How The Imamune System Mintains Food tolerance and, in the case of parasitic infections, Highlight the Specific Imamune Mechanisms That Can Go Awry.

“It’s Important To Note That Our Findings of Not Suggest That Worm Infections Trigger Food Allergies,” Clarifies Mucida, Head of the Laboratory of Mucosal Immunology. “They Reduce Tolerance Mechanisms While the Imamune Response Focuses on Dealing with the Worms.”

While These Findings Aren’t Directly Relevant to Food Allergies, They from Lay Some Groundwork for Further Investigation Into Food 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,” Canesto Says.

NEXT, CANOSSO PLANS TO SHIFT HER FOCUS TOWARD EARLY LIFE, EXPLORING How Maternal-Neonatal Interactions Shape Food intolerance. “Most Allergies Develop Early in Life,” She says. “I Want to Focus on How Breast Milk and Maternal Exposure to Dietary Antigen May Influence to Baby’s Imamune System, Potentially Shaping Their Risk of Developing Food Allergies.”