Basophils beyond allergic and parasitic diseases

Abstract

Basophils bind IgE via FcεRI-αβγ2, which they uniquely share only with mast cells. In doing so, they can rapidly release mediators that are hallmark of allergic disease. This fundamental similarity, along with some morphological features shared by the two cell types, has long brought into question the biological significance that basophils mediate beyond that of mast cells. Unlike mast cells, which mature and reside in tissues, basophils are released into circulation from the bone marrow (constituting 1% of leukocytes), only to infiltrate tissues under specific inflammatory conditions. Evidence is emerging that basophils mediate non-redundant roles in allergic disease and, unsuspectingly, are implicated in a variety of other pathologies [e.g., myocardial infarction, autoimmunity, chronic obstructive pulmonary disease, fibrosis, cancer, etc.]. Recent findings strengthen the notion that these cells mediate protection from parasitic infections, whereas related studies implicate basophils promoting wound healing. Central to these functions is the substantial evidence that human and mouse basophils are increasingly implicated as important sources of IL-4 and IL-13. Nonetheless, much remains unclear regarding the role of basophils in pathology vs. homeostasis. In this review, we discuss the dichotomous (protective and/or harmful) roles of basophils in a wide spectrum of non-allergic disorders.

Airway remodelling in asthma and the epithelium: on the edge of a new era

“…The combination of inflammatory and structural changes in airway remodelling provides the basis of what is canonically referred to as fixed airway obstruction. T2 inflammation, involving eosinophils, mast cells, ILC2s, Th2 cells and basophils, contributes to airway remodelling in most patients with severe asthma [ 128 , 186 , 187 ]. The contribution of non-T2 inflammation to airway remodelling, presumably involving mast cells, macrophages and neutrophils [ 49 , 63 ], remains to be fully clarified [ 186 , 188 , 189 ].…”

Basophils drive the resolution and promote wound healing in adult and aged mice

“…Basophils are pro-inflammatory cells involved in allergic diseases and protection against helminths, type 2 immune responses involving IgE reactivity (Miyake, Ito and Karasuyama, 2022; Poto et al ., 2023). However, type 2 immune responses have also evolved as a response to tissue damage which regulates tissue remodeling and healing(Gieseck, Wilson and Wynn, 2018), and are well known to antagonize and counterbalance type 1 immune responses against pathogens, and their toxicity for the tissues(Gause, Wynn and Allen, 2013).…”

“…However, basophils manifest both pro-inflammatory and pro-resolving properties in models of chronic skin allergic inflammation(Egawa et al ., 2013) or acute atopic dermatitis(Pellefigues, Naidoo, et al ., 2021). They can control the extent or amplitude of inflammation through various mechanisms(Miyake, Ito and Karasuyama, 2022; Poto et al ., 2023), including extracellular ATP degradation(Tsai et al ., 2015) and secretion of anti-inflammatory mediators such as retinoic acid(Hachem et al ., 2023), IL-10(Kleiner et al ., 2021), or the type 2 cytokines IL-4 and IL-13 (Pellefigues, Mehta, et al ., 2021). Basophils are the main source of IL-4 in models of helminth infection(van Panhuys et al ., 2011), atopic dermatitis(Pellefigues, Naidoo, et al ., 2021; Leyva-Castillo et al ., 2022; Takahashi et al ., 2023) or skin infection(Leyva-Castillo et al ., 2021).…”

Novel insights into the ontogeny of basophils

“…In these 10–20 years, researchers have developed an array of analytical tools for mouse basophils, such as basophil-depleting antibodies, engineered mice that can specifically deplete basophils, basophil reporter mice, and basophil-specific Cre-expressing mice ( Table 1 ) ( 4 – 16 ). Under such tools, basophils are now found to play a critical role in various immune reactions, including chronic allergic inflammation, protective immunity against parasites, autoimmune reactions, and tumor immunity ( 17 – 20 ). Recent advancements in single-cell transcriptomic techniques have shed new light on the understanding of basophil biology.…”