The discovery of special dendritic cells shed light on food allergy prevention

The immune system needs to be able to quickly attack invaders like viruses, but it can ignore harmless stimuli and cause allergies. Immune cells are known to ignore or “bear” molecules found in healthy cells in the body, for example. It is unclear how the system will achieve the latter.

Now, a new study led by researchers at NYU Langone Health reveals that special groups of cells in the intestine suppress the immune response caused by exposure to food proteins. These cells, known as “tolerant dendritic cells,” allow food to pass through the body without causing an immune response, unless it malfunctions to cause an allergy.

Cells also require the protein retinoic acid-associated orphan receptor-GAMMA-T (RORγT) and PR domain-containing 16 (PRDM16), which was found to effectively protect tolerant proteins from immune cells and protein inhalation (PRDM16) (PRDM16) (PRDM16)inflammation). Without proper functioning resistant cells, mice in this study were prone to developing food allergies and asthma.

Previous studies by the team revealed that these same cells control immune resistance to friendly intestinal bacteria, helping humans digest food and control the function of multiple organ systems. However, at the time, researchers had little knowledge of their identity or whether these cells controlled resistance to others.

Our study shows that RORγT-expressing dendritic cells are important components of immune modulatory responses that prevent food allergies. ”

Dan Littman, MD, PhD, Senior Research Author, Professor of Molecular Immunology in The Helen L. and Martin S. Kimmel Pathology Department, Professor of Cell Biology, NYU Grossman School of Medicine

“This finding adds evidence to previous research showing that these cells also maintain peace with the vastness. Microbiomethe mixture of microorganisms that live in our bodies may be important to prevent autoimmune conditions like Crohn's disease,” said Littman, who is also an investigator at the Howard Hughes Medical Institute.

By analyzing genes and proteins, these cells are expressed and compared to well-understood cell types, researchers concluded that they are a type of immune cell called dendritic cells. Usually, dendritic cells show small fragments of biological substances (known as antigens) to be notified by other immune cells called T cells. This program the T cells to initiate an immune attack the next time they encounter the antigen.

However, the researchers have shown that when chlorinated dendritic cells present antigens from food or flexible microorganisms to T cells, they become T cells. Anti-inflammatoryor “regulation.” This means that the next time T cells encounter an antigen, they suppress nearby inflammation instead of attacking them.

Published in journals Nature Online April 14th, the study showed that mice without salt-resistant dendritic cells had fewer regulatory T cells ready to prevent inflammation caused by food or microbial antigens. These mice also had inflammatory T cells that caused allergies and inflammation when exposed to their antigens.

Another important finding from this paper is that researchers have discovered human equivalents of chlorinated dendritic cells by analyzing human intestinal tissue and public sequencing datasets. Littman says it is not yet clear how abundant these cells are within the human body or whether they are involved in other forms of immune resistance outside the intestine. However, these questions are easy to answer as researchers have comprehensively identified cells in new research.

“If further experiments are successful, our findings could lead to innovative ways to treat food allergies,” Littman said. “For example, if someone has a peanut allergy, they can probably use tolerant dendritic cells to create more regulatory T cells and suppress an allergic reaction to peanut molecules.”

Moving forward, Littman said researchers wanted to understand more deeply how and where chlorinated dendritic cells in the body develop, and what signals they need to receive to perform their functions.

Funding for this study was provided by National Institutes of Health Grants P30CA016087, R01AI158687, T32AL100853, F32AI181496, and K08CA283272.

In addition to Littman, other NYU Langone researchers involved in this study include co-authors Liuhui Fu, Rabi Upadhyay and Maria Pokrovskii. co-authors Francis Chen, Gabriela Romero Meza and Adam Griezmer.

Littman is a co-founder of Vendanta Biosciences and Immunai and serves on the boards of Imidomics, Sonoma Biotherapeutics, Nilo Therapeutics, Evommune, and the board of directors of Pfizer Inc.

None of these groups were involved in the current study. The conditions for these relationships are managed according to NYU Langone Health policies and procedures.