RORγt+ Antigen-Presenting Cells: Pioneers of Food Tolerance
Understanding food tolerance is a crucial aspect of maintaining gut health, especially in a world where food allergies and intolerances are on the rise. Recent findings shed light on the role of RORγt+ antigen-presenting cells (APCs) in mediating this essential function.
The Role of pTreg Cells in Food Tolerance
Oral tolerance to food antigens and microbiota is maintained by peripherally induced regulatory T (pTreg) cells, which play a vital role in suppressing inflammatory responses within the gut. However, a significant question remains: which subsets of APCs actively instruct these regulatory responses versus inflammatory T cell responses?
Unveiling RORγt+ APCs
The spotlight is now on RORγt+ APCs, including group 3 innate lymphoid cells (ILC3s) and various non-ILC3 dendritic cell-like populations, such as extrathymic AIRE-expressing cells (eTACs), Thetis cells, and Janus cells. These cells have previously been implicated in shaping host-microbiota interactions within the gut source.
Recent Discoveries
Five landmark studies have recently emerged, illustrating the pivotal role these RORγt+ APCs play in inducing food-antigen-specific pTreg cells and establishing food tolerance.
Key Findings from Recent Research
Transcription Factors Required: Research led by Fu et al. revealed that RORγt+ APCs require transcription factors PRDM16 and RORγt for development. Intriguingly, the epigenetic and transcriptional profiles of these cells are more akin to conventional dendritic cells (cDCs) than to ILC3s, leading the team to refer to this DC-like population as PRDM16+RORγt+ tolerizing DCs (tolDCs).
- Impact on Gut Immunity: Mice devoid of tolDCs exhibited increased levels of intestinal T helper 2 (TH2) cells and signs of spontaneous type 2 gastrointestinal pathology, suggesting a crucial role for tolDCs in preventing food allergies.
The Mechanism of Action
Using oral OVA (ovalbumin) administration as a model for food antigens, researchers demonstrated that tolDC-depleted mice showed a decrease in OVA-specific pTreg cells and an increase in OVA-specific TH2 and T follicular helper (TFH) cells. Notably, the protective effect of oral antigen tolerization was lost in these mice during models of both allergic lung inflammation and systemic anaphylaxis.
Insights from Human Samples
Moreover, a population of PRDM16+RORγt+ cells has been identified in human samples from mesenteric lymph nodes, intestinal lamina propria, and tonsils. This discovery adds another layer of significance, highlighting the translational potential of these findings for understanding human food tolerance mechanisms.
Conclusion
These recent studies underscore the fundamental role of RORγt+ APCs in the intricate dance of food tolerance and the prevention of allergic reactions. As research evolves, targeting these cells could pave the way for innovative therapies aimed at treating and preventing food allergies, ensuring a healthier future for individuals affected by these conditions.
For those interested in delving deeper into the world of immunology and food tolerance, consider exploring additional articles and studies available here.
Engaging in this critical discourse not only broadens our understanding of gut health but also empowers us to advocate for better prevention strategies and treatments in the realm of food allergies.
