The Gut’s Hidden Defenders: Tolerogenic Dendritic Cells

Scientists at NYU Langone Health have made a significant stride in understanding food allergies with the finding of a specialized type of immune cell residing in the intestine.These cells, termed tolerogenic dendritic cells, appear to be crucial in maintaining tolerance to food proteins, preventing the body from launching needless and harmful inflammatory responses.

How Tolerance Works: Rorγt and PRDM16

The immune system’s ability to differentiate between harmful pathogens and harmless substances like food is paramount for maintaining health. The recent study sheds light on the mechanisms behind this tolerance, revealing that tolerogenic dendritic cells rely on specific proteins to function correctly. These proteins include retinic acid receptor-gamma-t (Rorγt) and PR domains-containing 16 (PRDM16). These proteins are essential for the cells to effectively promote tolerance.

Mouse Model Insights: A Link to Allergies and Asthma

To investigate the role of these cells, researchers conducted experiments with mice. The results were compelling: mice lacking tolerogenic dendritic cells exhibited a heightened susceptibility to both food allergies and asthma. This finding underscores the importance of these cells in maintaining immune homeostasis within the gut.

Previous research by the same team had already established that these cells play a role in controlling immune tolerance to beneficial gut bacteria,which are vital for digestion and the proper functioning of various organ systems. This highlights the multifaceted role of these cells in maintaining overall health.

The Study’s Key Findings: Regulatory vs. Inflammatory T Cells

The research, published in the journal *Nature*, details how the absence of tolerogenic dendritic cells impacts the balance of T cells in the body. Mice lacking these cells had fewer regulatory T cells, which are responsible for preventing inflammation triggered by food or microbial antigens. Conversely, they had an increased number of inflammatory T cells, which are known to contribute to allergies and inflammation.

Mice without tolerogeneous dendritic cells had fewer regulatory T cells that prevent inflammation from food or microbial antigens. Instead, they had more inflammatory T cells that caused allergies and inflammation.

Human Relevance: Identifying Equivalent Cells

importantly, the researchers were able to identify human equivalents of these tolerogenic dendritic cells through the analysis of human intestinal tissue and publicly available sequencing data records. This discovery suggests that the findings in mice may be applicable to humans, opening avenues for potential therapeutic interventions.

However, questions remain about the prevalence of these cells in the human body and whether they play a role in other forms of immune tolerance beyond the intestine. further research is needed to fully understand their function in humans.

Future Directions: Potential Therapies and Further Research

The researchers are optimistic that their discoveries could pave the way for innovative treatment methods for food allergies. One potential approach involves increasing the number of regulatory T cells in individuals with allergies, such as peanut allergies, to suppress the allergic reaction to peanut molecules.

Looking ahead, the research team plans to delve deeper into understanding how and where tolerogenic dendritic cells develop in the body and what signals they require to perform their critical function. This knowledge could lead to targeted therapies that promote the advancement and function of these cells, ultimately preventing or treating food allergies.

In the future, the researchers want to better understand how and where tolerogical dendritic cells develop in the body and what signals they need to perform their function.

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