Antigen-presenting cells as arbiters of mucosal tolerance and immunity

Within the intestine, the immune system encounters a vast array of microbial antigens, as well as dietary components. Antigen-presenting cells (APCs) play a critical role in tailoring an appropriate immune response, ensuring both tolerance to innocuous antigens and protection from pathogens. An explosion of single-cell transcriptomic studies has revealed new subsets of APCs within mucosal tissues and lymph nodes, most notably within the gut. Harnessing their full potential to elicit protective immunity during oral vaccination or restoration of tolerance in inflammatory or allergic diseases requires an in-depth understanding of their unique functional roles and differentiation programs. Here we review the growing understanding of APC heterogeneity and discuss how balance and cooperation between distinct subsets shape mucosal immunity, inflammation and tolerance.