Editorial: Mast cells in health, disease and forensic practice: a mystery not yet revealed

Classical Hodgkin lymphoma (CHL) accounts for 10% of all lymphomas ( 4 ). Among histological subtypes, nodular sclerosis and mixed cellularity account for nearly 80% of all CHL cases. Since the increase in MCs in CHL appears to be greater in nodular sclerosis than in other subtypes of CHL and a correlation between the degree of angiogenesis and the number of MCs in CHL has been demonstrated, Ribatti et al. propose that MCs are considered possible new targets for disease treatment since novel therapies acting on these cell types inhibit angiogenesis and tissue remodeling and allow the secretion of cytotoxic cytokines such as Tumor Necrosis Factor. Chronic rhinosinusitis with nasal polyposis (CRSwNP) a type 2 disease gives rise to polyps that block the sinuses and nostrils, leading to severe congestion, nasal discharge, pain, or pressure on the face, and reduction of smell and taste ( 5 ). Nasal cytology demonstrated that CRSwNP is characterized not only by eosinophilic but also MC inflammation and, in particular, the most severe forms of CRSwNP are characterized precisely by mixed eosinophilic-mast cell inflammation. Therefore, Gelardi et al. open the possibility for new therapies aimed at reducing both eosinophil and MC infiltration.

Recent advances in developmental immunology have revealed a hematopoietic stem cell (HSC)-independent origin for various cell types, including MCs. It is now established that the physiological production of MCs in the aorta-gonad-mesonephros (AGM) region is mostly completed before birth. However, if the AGM region represents an important site of MC generation during ontogeny, it is unknown whether the first HSC emerging in the AGM or fetal liver (FL) possess the potential to regenerate MCs. Yoshimoto et al. demonstrated through sophisticated experiments that the first HSCs that emerge in the AGM and infiltrate the first FL can produce MCs, but only during a short time window. The influence of estrogen on MC function has also been recognized as a potential factor in endometriosis ( 6 ). McCallion et al. demonstrates a significant increase in the number of MCs within the endometriotic lesions compared to the corresponding eutopic endometrium of the same patients. Furthermore, an increase in SCF (essential for MC development) was found in endometriotic lesions while genetic analysis revealed a microenvironment favoring MC recruitment and subsequent differentiation. Cocultures of endometriotic epithelial cells and endometrial stromal cells incubated with MC-conditioned media showed a significant increase in the production of proinflammatory cytokines by these cells. Endometriotic lesions produced in C57BL/6 mice, confirm essentially previous findings in human. These results suggest that endometriotic lesions provide a microenvironment necessary for MC recruitment and differentiation in which the same cells release pro-inflammatory mediators that contribute to disease progression. Savages et al. using primary human lung fibroblasts (HLF), demonstrate that isolated and labeled exosomes from the human mast cell line as well as TGF-β have an additive effect on collagen synthesis in HLF and this fact could represent a unique paradigm for understanding fibrosis. The authors state that these findings provide rationale for targeting multiple fibrogenic pathways in the management of pulmonary fibrosis and for the use of MC exosomes as a biomarker for the prognostic and diagnostic management of evolving fibrotic lung disease as reported in patients with severe COVID-19.

This topic was the occasion for a meeting of expert scientists, coming from different schools around the world, whose research field is aimed toward understanding MC biology. The reviews have proved to be punctual in the clarity and exposition, the research articles have proposed new methods and field of research that will certainly be deepened in the near future. In conclusion, from this topic emerges the idea that the issue of MCs biology is extremely important and therefore the idea that the “mystery” of MCs is far from solved is confirmed.

SB: Writing—review and editing. DR: Writing—review and editing. JB: Writing—review and editing.