Basophils in allergic immune responses
Highlights
► Basophils mainly act as effectors rather than initiators of allergic reactions. ► IgE-mediated chronic allergic inflammation of murine skin is basophil-dependent. ► Novel basophil-deficient mouse strains help to define the role of basophils in vivo.
Introduction
Basophils are the least abundant type of granulocytes after neutrophils and eosinophils. They mature in the bone marrow and have a lifespan of about 60 h under steady-state conditions in mice [1]. Basophils are morphologically and functionally very similar to tissue-resident mast cells. Both cell types contain granules that can be stained with basophilic aniline dyes. They both express the αβγ2 form of the high-affinity receptor for IgE (FcɛRI). Interestingly, FcɛRI can also be expressed as signaling competent αγ2 form by subsets of dendritic cells [2, 3••, 4], monocytes [5] and eosinophils [6]. Effector molecules produced by mast cells and basophils include vasodilators like histamine and platelet-activating factor (PAF), leukotriene C4 and the Th2-associated cytokines IL-4 and IL-13 [7]. However, basophils represent a distinct cell lineage and are not a population of immature circulating mast cells.
Section snippets
The early type 2 immune response – are basophils crucial for Th2 polarization?
In analogy to Th1 polarization where early secretion of IL-12 by DCs initiates the Th1 differentiation program it was proposed that an innate source of IL-4 is required for Th2 polarization. Several reports pointed toward an important role for basophils as inducers of Th2 polarization. Mice deficient for interferon response factor 2 (IRF2) or the tyrosine kinase Lyn show increased levels of circulating basophils and a spontaneously Th2-biased phenotype [8, 9]. Furthermore, basophils are
Basophil mobilization and activation by cytokines
Basophils respond to different cytokines that modulate their survival, effector functions and tissue recruitment. IL-3 from T cells is important for basophilia during helminth infection, although IL-3 is not essential for basophil development under steady-state conditions [19, 20]. Basophils also express IL-3 and may thereby regulate their survival in an autocrine manner [21]. In addition, IL-3 exerts an important co-stimulatory function for mediator release. IL-3, IL-18 or IL-33 are potent
Basophils in allergic skin reactions
The recruitment of basophils during allergic skin reactions has been observed in early studies with guinea pigs that developed a ‘cutaneous basophil hypersensitivity’ reaction upon injection of protein antigen with incomplete Freund's adjuvant [27]. Basophils were also identified in human skin of allergic contact dermatitis patients [28] and in allergen-induced patch test sites of atopic dermatitis patients [29]. Basophils are found in skin biopsies and blister fluid of cutaneous late-phase
Basophils in asthma and allergic rhinitis
Basophils were found in large numbers in post-mortem biopsies of fatal asthma [42, 43]. Accumulation of basophils was also observed in bronchial biopsies of atopic asthma patients [44] and nasal washes of allergic rhinitis patients [45]. Basophils probably contribute to pathology since they are the main source of histamine during the late phase response (LPR) after nasal challenge of seasonal allergic rhinitis patients [46]. However, a short-term allergic inflammation model of the murine lung
Basophils and anaphylaxis
Anaphylaxis is a severe systemic allergic response characterized by rapid drop of blood pressure, shortness of breath, reduced body temperature and loss of consciousness. The classical form of anaphylaxis is mediated by histamine released from mast cells that are activated by allergens via crosslinking of surface-bound IgE molecules. Basophils were reported to be responsible for an alternative form of anaphylaxis that is mediated by platelet activating factor (PAF) released from basophils after
Conclusion
Basophil in vivo functions were ignored for a long time owing to their low frequency and lack of specific markers. The observation that basophils can be depleted with antibodies that bind to activating receptors on basophils and mast cells enabled researchers to address the role of basophils in mouse models. Some of these studies proposed that basophils act early during type 2 immune responses as crucial antigen-presenting cells for polarization of Th2 cells. More recent studies with different
References and recommended reading
Papers of particular interest, published within the period of review, have been highlighted as:
•• of outstanding interest
Acknowledgements
This work was supported by an ERC starting grant (PAS 241506) from the European Union and by an Emmy Noether grant (Vo944/2-2) from the Deutsche Forschungsgemeinschaft.
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