The transcriptional program, functional heterogeneity, and clinical targeting of mast cells

Abstract

Cildir et al. discuss the recent findings in transcriptional regulation of mast cell development and activation and provide insights into the plasticity and clinical targeting of mast cell functions.

Targeting tumor-resident mast cells for effective anti-melanoma immune responses

“…In particular, there is growing evidence that innate immune cells, such as MCs, and especially their plasticity are relevant in cancer progression (45). MCs, known for their detrimental effects in allergy and anaphylaxis (46), are in fact multifunctional cells and play a key role in certain immune responses (22,47). They are located at strategically important sites, predominantly at interfaces to the microenvironment, and possess phenotypic and functional heterogeneity as they achieve their terminal differentiation and maturation dependent on the tissue's microenvironment (48).…”

The histone deacetylase inhibitor valproic acid attenuates phospholipase Cγ2 and IgE-mediated mast cell activation

“…Therefore, the development of new therapies that enable the regulation of mast cell activation is a priority in allergic diseases. In this line, several approaches are under investigation, including the targeting of activating mast cell‐surface receptors or cell‐signaling molecules that participate in FcεRI mediated‐activation as well as the engagement of mast cell inhibitory receptors 6 …”

Mechanisms of allergen-specific immunotherapy for allergic rhinitis and food allergies

“…Apart from Th2 cells, follicular helper T (Tfh) cells originated from the germinal centre of the lymph node are another source of IL-4 that contributes to the class-switching to IgE in B cells [6]. During isotype switching, certain B cell subsets become plasma cells, switching from IgM to IgE production and these IgE binds to the high-affinity receptor for IgE (FcεRI) expressed on the surface of mast cells (MCs) and basophils, resulting in sensitization [33,34].…”

“…IL-4, IL-13) and chemokines (eg. CCL3) orchestrated by several transcription factors [33,[36][37][38][39][40][41][42][43][44] including nuclear factor-κ B (NF-κB) which is the master regulator of immunity, inflammatory response [45][46][47] and cell survival [48][49][50][51][52][53]. For instance, expression of IL-6 in activated MCs is mediated by NF-κB [54] while that of TNFα and IL-13 in activated MCs requires nuclear factor of activated T cells (NFAT) [55].…”