Mouse research reveals modern technique to probably handle allergy threat
By Marta Wegorzewska
More often than not, the intestinal immune system can acknowledge pal from foe, tolerating myriad meals whereas destroying disease-causing invaders. However for about 30 million Individuals with meals allergic reactions – together with 4 million youngsters – immune cells mistakenly determine meals as a risk, triggering probably life-threatening reactions.
Now, researchers at Washington College Faculty of Drugs in St. Louis have recognized, in mice, that important immune cells within the gut forestall an unwarranted assault in opposition to innocent meals allergens. Within the absence of such cells, mice skilled intestine irritation and an allergic response to meals.
Their analysis was revealed on-line April 3 in Cell and can seem in print Could 15.
“We’re seeing a speedy international enhance in meals allergic reactions that considerably impression high quality of life,” mentioned Marco Colonna, MD, the Robert Rock Belliveau, MD, Professor of Pathology at WashU Drugs. “The dearth of therapeutics to forestall and handle meals allergic reactions complicates the rising public well being subject. Now that we all know the gamers that set up tolerance to meals allergens, we are able to devise modern methods to focus on them therapeutically and probably forestall or deal with meals allergic reactions.”
The immune system encounters frequent meals allergens – peanuts, tree nuts, milk, eggs and shellfish, amongst others – with out launching a self-sabotaging immune assault in a course of referred to as tolerance. Damaged tolerance to meals triggers an allergic response with signs starting from gentle hives and itching to a extreme, life-threatening allergic response that may trigger throat swelling and problem respiration and requires quick therapy. As half of the present research, the researchers aimed to house in on the gamers working to forestall such reactions, in work that will assist develop preventive therapies for meals allergic reactions.
Tolerance to meals entails a number of immune cells. Sure immune cells decide up meals particles, chop them into fragments and current them to the immune system’s T cells, instructing these cells to stay unresponsive to the innocent intruder. Extra not too long ago, a small inhabitants of cells – the RORγt+ dendritic cells – has been discovered among the many intestine’s presenting immune cells in a number of species. Colonna’s lab was the primary to determine the cells in individuals in 2023. Their position in stopping meals allergic reactions had not been explored.
Patrick Rodrigues, PhD, a postdoctoral scholar, and Shitong Wu, an MD/PhD pupil, in Colonna’s lab and the research’s co-first authors, got down to perceive whether or not RORγt+ dendritic cells are the intestine’s immune cells that forestall meals allergic reactions. They handled mice with ovalbumin, a extremely allergenic protein present in egg whites, orally after which intranasally. Mice missing intestine RORγt+ dendritic cells confirmed indicators of allergic lung irritation, whereas mice with these cells didn’t. An evaluation of the intestine immune cells discovered an imbalance among the many T cells that set off versus dampen immune responses to meals particles within the allergic mice, with a skewing towards the previous.
“By eradicating RORγt+ dendritic cells from the intestine in mice, we broke tolerance to meals allergens,” mentioned Rodrigues. “The invention is now inspiring us to see if we are able to do the alternative: forestall meals allergic reactions by supporting the exercise of this cell inhabitants. As a result of RORγt+ dendritic cells are present in individuals, our discovering presents an thrilling new chance to handle meals allergic reactions and different gut-related immune ailments resembling celiac illness or inflammatory bowel illness.”
Lately, the FDA permitted an injectable treatment, that, if administered constantly, helps forestall an allergic response to unintended publicity to small quantities of allergens by blocking the antibodies that consequence from an activated immune response. Avoiding the allergen and carrying an EpiPen continues to be really useful for people on the treatment.
“Concentrating on the exercise of RORγt+ dendritic cells has the potential to work even additional upstream to forestall an immune response from first being triggered,” mentioned Wu. “If that proves to be true, a remedy supporting the exercise of this small inhabitants of cells may provide lasting tolerance to meals allergens.”
Rodrigues PF, Wu S, Trsan T, Panda SK, Fachi JL, Liu Y, Du S, de Oliveira S, Antonova AU, Khantakova D, Sudan R, Desai P, Diamond MS, Gilfillan S, Anderson SK, Cella M, Marco Colonna. Rorγt-positive dendritic cells are required for the induction of peripheral Tregs in response to oral antigens. Cell. April 3, 2025. DOI: 10.1016/j.cell.2025.03.020
This work was supported by the Nationwide Institutes of Well being (NIH), grant numbers RO1AI134035, RO1DK132327, RO1DK126969, RO1DK124699, T32DK077653; and the Swiss Nationwide Science Basis (SNF), grant numbers P2BSP3_191754/P500PB_211033. This content material is solely the accountability of the authors and doesn’t essentially signify the official views of the NIH.
About Washington College Faculty of Drugs
WashU Drugs is a world chief in educational medication, together with biomedical analysis, affected person care and academic applications with 2,900 school. Its Nationwide Institutes of Well being (NIH) analysis funding portfolio is the second largest amongst U.S. medical faculties and has grown 56% within the final seven years. Along with institutional funding, WashU Drugs commits nicely over $1 billion yearly to fundamental and medical analysis innovation and coaching. Its school follow is persistently throughout the high 5 within the nation, with greater than 1,900 school physicians training at 130 places and who’re additionally the medical staffs of Barnes-Jewish and St. Louis Kids’s hospitals of BJC HealthCare. WashU Drugs has a storied historical past in MD/PhD coaching, not too long ago devoted $100 million to scholarships and curriculum renewal for its medical college students, and is house to top-notch coaching applications in each medical subspecialty in addition to bodily remedy, occupational remedy, and audiology and communications sciences.
