A study published in Science sheds light on the intricate workings of the intestinal immune system, revealing how it distinguishes between harmful pathogens and beneficial food particles. Led by Maria C.C. Canesso from Rockefeller University, the research identifies specific gut cell types that communicate with T cells, directing them to tolerate, attack, or ignore various substances.
The study focuses on antigen presenting cells (APCs) and their role in instructing T cells. Two types of APCs, cDC1s and Rorγt+ APCs, were found to be primarily responsible for promoting tolerance. These cells capture dietary antigens from ingested food and present them to T cells, giving rise to pTregs that ensure food tolerance.
Canesso and her team utilized an advanced technology called LIPSTIC, developed by the Victora lab, to catalogue cell-to-cell interactions. This technological breakthrough allowed researchers to understand immune cell dynamics that were previously impossible to observe.
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The study also explored how intestinal infections can disrupt the balance of tolerance. Experiments with mice infected by the parasitic worm Strongyloides venezuelensis demonstrated a shift away from tolerance-promoting APCs toward those that promote inflammation. This resulted in reduced tolerance toward dietary proteins and signs of allergy when challenged.
The researchers identified key cytokines and pathways influencing how APCs present antigens and modulate immune responses. For instance, the infection induced a surge in pro-inflammatory cytokines such as IL-6 and IL-12, which have been shown to push APC activity toward inflammatory outcomes.
While these findings don't directly explain food allergies, they provide a foundation 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,” Canesso says.