Basophil differentiation, heterogeneity, and functional implications.

Allergen-stimulated basophils secrete leukotriene C4 (LTC4), acting on the cysteinyl leukotriene receptor (CysLTR2) in neurons, activating neuronal signaling that mediates acute itch exacerbation in atopic dermatitis (AD). CXCR2+ basophils recruited to the kidney release interleukin (IL)-6, which recruits type 17 T helper (T H 17) cells, contributing to the pathogenesis of renal fibrosis. Targeting CXCR2+ basophils might be considered a therapeutic strategy in renal fibrosis. In mouse bone marrow granulocyte–monocyte progenitors, high expression of E-cadherin on myeloid progenitors marks an early population of pro-basophil and mast cell progenitors, which is committed to the basophil and mast cell fates. Lung-resident basophils establish a lung-specific function influenced by IL-33 and granulocyte–macrophage colony-stimulating factor (GM-CSF), which are crucial for maintaining alveolar macrophage development and function. Basophils serve as multifunctional regulators in either maintaining homeostasis or contributing to disease pathogenesis. Recent findings highlight their diverse lineage-priming stages and involvement in disorders across organs such as the skin, lung, kidney, and heart, suggesting systemic influence and potential heterogeneous subpopulations. However, the underlying mechanisms of basophil differentiation and heterogeneity remain unclear, meriting further investigation, particularly when developing possible therapeutic strategies for relevant disorders. Basophils, rare granulocytes, have long been acknowledged for their roles in type 2 immune responses. However, the mechanisms by which basophils adapt their functions to diverse mammalian microenvironments remain unclear. Recent advancements in specific research tools and single-cell-based technologies have greatly enhanced our understanding of basophils. Several studies have shown that basophils play a role in maintaining homeostasis but can also contribute to pathology in various tissues and organs, including skin, lung, and others. Here, we provide an overview of recent basophil research, including cell development, characteristics, and functions. Based on an increasing understanding of basophil biology, we suggest that the precise targeting of basophil features might be beneficial in alleviating certain pathologies such as asthma, atopic dermatitis (AD), and others. [ABSTRACT FROM AUTHOR]