Mast cells (MCs) are tissue-resident immune cells distributed in all tissues and strategically located close to blood and lymphatic vessels and nerves. Thanks to the expression of a wide array of receptors, MCs act as tissue sentinels, able to detect the presence of bacteria and parasites and to respond to different environmental stimuli. MCs originate from bone marrow (BM) progenitors that enter the circulation and mature in peripheral organs under the influence of microenvironment factors, thus differentiating into heterogeneous tissue-specific subsets. Even though MC activation has been traditionally linked to IgE-mediated allergic reactions, a role for these cells in other pathological conditions including tumor progression has recently emerged. However, several aspects of MC biology remain to be clarified. The advent of single-cell RNA sequencing platforms has provided the opportunity to understand MCs’ origin and differentiation as well as their phenotype and functions within different tissues, including the gut. This review recapitulates how single-cell transcriptomic studies provided insight into MC development as well as into the functional role of intestinal MC subsets in health and disease.

Mast cells (MCs) are essential components of the immune system that enter the circulation as immature bone marrow progenitors and differentiate in peripheral organs under the influence of microenvironment factors. As tissue-resident secretory immune cells, MCs rapidly detect the presence of bacteria and parasites because they harbor many surface receptors, which enable their activation via a multitude of stimuli. MC activation has been traditionally linked to IgE-mediated allergic reactions, but MCs play a pivotal role in different physiological and pathological processes. In gut, MCs are essential for the maintenance of gastrointestinal (GI) barrier function, and their interactions with neurons, immune cells, and epithelial cells have been related to various GI disorders. This review recapitulates intestinal MC roles in diseases with a main focus on inflammatory bowel disease (IBD) and irritable bowel syndrome (IBS). Emerging therapies targeting MCs and their mediators in clinical practices will also be discussed.

Mast cells are tissue-resident immune cells distributed in all tissues and strategically located close to blood and lymphatic vessels and nerves. Thanks to the expression of a wide array of receptors, mast cells act as tissue sentinels, able to detect the presence of bacteria and parasites and to respond to different environmental stimuli. Mast cells originate from bone marrow progenitors that enter the circulation and mature in peripheral organs under the influence of microenvironment factors, thus differentiating in heterogeneous tissue-specific subsets. Even though mast cell activation has been traditionally linked to IgE-mediated allergic reactions, a role for these cells in other pathological conditions including tumor progression has recently emerged. However, several aspects of mast cell biology remain to be clarified. The advent of single-cell RNA sequencing platforms has provided the opportunity to understand mast cell origin and differentiation as well as the phenotype and functions within different tissues, including the gut. This review recapitulates how single cell transcriptomic studies provided insight into mast cell development as well as into the functional role of intestinal MC subsets in health and disease.

Food allergy is an increasing global health burden, particularly in industrialized countries, with rising prevalence in both pediatric and adult populations. It is characterized by exaggerated immune responses to innocuous dietary antigens, leading to clinical manifestations ranging from mild gastrointestinal symptoms to life-threatening anaphylaxis. Mast cells are central effectors in the pathophysiology of food allergy, initiating and amplifying allergic inflammation through the release of a broad array of mediators upon activation. Recent studies have revealed that the intestinal microbiota plays a critical role in shaping immune responses, including the regulation of mast cell development, maturation, and activation. Moreover, dysbiosis has been associated with increased susceptibility to allergic sensitization and heightened mast cell reactivity. This review explores the molecular mechanisms underlying the microbiota–mast cell axis in the context of intestinal homeostasis and food allergy with a particular emphasis on the regulation of mast cell effector functions by TLR signaling and microbial metabolites. We also discuss the therapeutic potential of targeting the microbiota–mast cell axis as novel strategies to restore immune tolerance. Understanding this complex crosstalk opens new avenues for translational approaches in the prevention and treatment of food allergy.

Mast cells (MCs) are multifunctional immune cells with context-dependent functions in cancer. In colorectal cancer (CRC), their contribution remains debated, suggesting that distinct MC subsets may either support tumor progression or promote anti-tumor immunity. Using single-cell RNA sequencing in a mouse model of inflammation-driven CRC, we uncovered extensive MC plasticity during tumor progression. Transcriptomic profiling and pseudotime trajectory analysis revealed a transition from precursor-like MCs exclusively present in adjacent tissue to differentiated tumor-associated MC (TAMC) subsets. TAMCs displayed a distinct repertoire of proteases and pro-inflammatory cytokines, contributing to increased vascular permeability and recruitment of additional immune cells. Moreover, TAMCs exhibited upregulation of molecules with immunosuppressive potential and underwent a tumor microenvironment (TME)-driven metabolic reprogramming. Accordingly, antibody-mediated MC depletion reduced tumor burden. Notably, most of the transcriptional features identified in a murine CRC model were recapitulated in human CRC, supporting the translational relevance of this MC program. Our findings identify a tumor-adapted MC state that orchestrates immune evasion and tissue remodeling during CRC progression, supporting the notion that MC are reprogrammed toward an immune-suppressive and pro-tumorigenic phenotype.