Basophils Play a Critical Role in the Development of IgE-Mediated Chronic Allergic Inflammation Independently of T Cells and Mast Cells

Mukai, Kaori; Matsuoka, Kunie; Taya, Choji; Suzuki, Hidenori; Yokozeki, Hiroo; Nishioka, Kiyoshi; Hirokawa, Katsuíku; Etori, Maki; Yamashita, Makoto; Kubota, Toshiyuki; Minegishi, Yoshiyuki; Yonekawa, Hiromichi; Karasuyama, Hajime

doi:10.1016/j.immuni.2005.06.011

Cited by 288 publications

(327 citation statements)

References 51 publications

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“…As shown here, and as corroborated in other models of cutaneous hypersensitivity (Mukai et al, 2005), we found no effects on eosinophil or Gr-1 + infiltrates in mast cell-deficient mice (Fig. 1 E …”

Section: Basophils Demonstrate Activation-dependent Interactions Withsupporting

confidence: 90%

“…More recent approaches have coupled robust genetic and immunological tools that have allowed increasing resolution of the mechanisms involved in IgE-mediated allergic dermatitis. By using transgenic mice overexpressing antigen-specific IgE or passive transfer, together with antibody-mediated depletion of basophils, Mukai et al (2005) demonstrated a requirement for basophils in IgEmediated dermatitis. Subsequent work using genetic approaches to eliminate basophils confirmed these findings (Ohnmacht et al, 2010;Jin et al, 2012;Matsuoka et al, 2013).…”

Section: Discussionmentioning

confidence: 99%

“…However, recent studies in a variety of models suggest an unexpected contribution of circulating basophils to allergic inflammatory responses, including the accumulation of eosinophils in target tissues (Mukai et al, 2005;Ohnmacht et al, 2010;Jin et al, 2012;Matsuoka et al, 2013). How circulating basophils influence localized eosinophil recruitment is unclear, but elucidation of this pathway could uncover new strategies for regulating allergic inflammation.…”

Section: Ige-basophil Interactions Act As An Inflammatory Switch To Pmentioning

confidence: 99%

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IgE-activated basophils regulate eosinophil tissue entry by modulating endothelial function

Cheng¹,

Sullivan²,

Retana³

et al. 2015

J Cell Biol

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Vertebrate immunity has evolved a modular architecture in response to perturbations. Allergic inflammation represents such a module, with signature features of antigen-specific IgE and tissue eosinophilia, although the cellular and molecular circuitry coupling these responses remains unclear. Here, we use genetic and imaging approaches in models of IgEdependent eosinophilic dermatitis to demonstrate a requisite role for basophils. After antigenic inflammation, basophils initiate transmigration like other granulocytes but, upon activation via their high-affinity IgE receptor, alter their migratory kinetics to persist at the endothelium. Prolonged basophil-endothelial interactions, in part dependent on activation of focal adhesion kinases, promote delivery of basophil-derived IL-4 to the endothelium and subsequent induction of endothelial vascular cell adhesion molecule-1 (VCAM-1), which is required for eosinophil accumulation. Thus, basophils are gatekeepers that link adaptive immunity with innate effector programs by altering access to tissue sites by activation-induced interactions with the endothelium.

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Section: Basophils Demonstrate Activation-dependent Interactions Withsupporting

confidence: 90%

Section: Discussionmentioning

confidence: 99%

Section: Ige-basophil Interactions Act As An Inflammatory Switch To Pmentioning

confidence: 99%

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IgE-activated basophils regulate eosinophil tissue entry by modulating endothelial function

Cheng¹,

Sullivan²,

Retana³

et al. 2015

J Cell Biol

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“…18 Treatment with a basophil-depleting Abs prevents the development of IgE-CAI, 42 indicating the essential role of basophils in this reaction. Our prior study showed that the number of infiltrative basophils in skin lesions of IgE-CAI was higher than that of dermal mast cells (19.4 cells/mm 2 versus 8.2 cells/mm 2 ).…”

Section: Discussionmentioning

confidence: 99%

“…18 -21 Basophils initiate IgE-mediated, chronic, cutaneous allergic inflammation (IgE-CAI). 18 They also elicit IgG-but not IgE-mediated anaphylaxis. 19 Basophils promote antigen-specific Th2 development 20 and augment humoral memory responses.…”

mentioning

confidence: 99%

FcεRI, but Not FcγR, Signals Induce Prostaglandin D2 and E2 Production from Basophils

Ugajin

Satoh

Kanamori

et al. 2011

The American Journal of Pathology

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Prostaglandin (PG) D2 and PGE2 are arachidonic acid metabolites that are generated though an isomerization reaction catalyzed by PG synthases. PGs have been implicated in immunologic reactions in addition to a wide range of physiological functions. It has long been thought that basophils, in contrast to mast cells, do not synthesize PGs, although they do release leukotrienes and platelet-activating factor. Here, we show that basophils function as a source of PGD2 and PGE2. In vitrocultured basophils from mouse bone marrow produced both PGD2 and PGE2 in response to IgE ؉ antigen (Ag), but not to IgG ؉ Ag. Release of PGs was almost completely abrogated in cultured basophils from FcR␥-chain ؊/؊ mice, indicating the involvement of Fc RI. Basophils freshly isolated from bone marrow cells (primary basophils) were also capable of secreting PGD2 and PGE2. Although the amount of PGD2 released from primary basophils was lower than that from mast cells, the capability of primary basophils to generate PGE2 was more potent than that of mast cells. Transcripts and proteins for both hematopoietic-type PGD synthase and PGE synthase were detected in basophils. In addition, human basophils, like mouse basophils, also produced PGD2 through IgE-mediated stimulation. Thus, basophils could be an important source of PGD2/ PGE2 and may contribute to allergic inflammation and immune responses. Prostaglandins, such as PGD2 and PGE2, are cyclooxygenase (COX) metabolites of arachidonic acids. They have a wide range of biological activities, including relaxation and contraction of smooth muscles, and modulation of neuronal activity. 1 PGD2 is principally produced by activated mast cells and, to a lesser extent, by T helper cell 2 (Th2) cells and dendritic cells 2-4 and exerts its effect through D prostanoid 5 and chemoattractant receptor-homologous molecule receptors expressed onTh2 lymphocytes (CRTH2). 6 A number of recent studies have shown that PGD2 is involved in inflammatory reactions. Mast cell-derived PGD2 suppresses IL-12 production by dendritic cells that induce Th2 responses in vivo. 7 PGD2 both activates and induces chemotaxis of Th2 cells, eosinophils, and basophils. 6 A large amount of PGD2 is detected in broncho-alveolar lavage fluid during allergen-induced airway inflammation. 8 Transgenic mice overexpressing human PGD synthase showed exacerbation of ovalbumin (OVA)-induced lung inflammation associated with pronounced eosinophilia and increased Th2 cytokine production. 9 In our previous studies, mice deficient in the CRTH2 gene were characterized by alleviated IgE-mediated cutaneous responses, contact hypersensitivity reactions, 10 and cedar pollen dermatitis. 11 However, PGE2 is produced by a variety of cells, including fibroblasts and macrophages, and exerts its effects via prostaglandin E2 (EP)1, EP2, EP3, and EP4 receptors. 12 PGE2 acts on T cells to enhance production of Th2-type cytokines and to inhibit production of Th1 cytokines in vitro, 13 whereas another study showed that PGE2 facilitates Th1 differentiation via EP...

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Generation and Characterization of Mouse Basophils from Bone Marrow and Purification of Basophils from Spleen

Yoshimoto

Nakanishi

2012

CP in Immunology

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Basophils are rare circulating granulocytes that originate from progenitor cells in the bone marrow and have been considered important effector cells in IgE-mediated allergic inflammation. Basophils constitute <1% of blood leukocytes and are usually absent or present only in small numbers in tissues. They may, however, be recruited to inflammatory sites when an antigen is present and contribute immediately to hypersensitivity reactions. Basophils can therefore serve as primary effector cells in allergic disorders. Despite a large pool of experimental evidence that has led to the discovery of these functional attributes of basophils, many questions regarding their contribution to these immune responses remain unanswered. This is due, in part, to the lack of methods for generation and purification of basophils and the lack of animal models appropriate for their functional analysis. Recent studies, however, have revealed a role for basophils as antigen-presenting cells that preferentially induce Th2 cells in response to complexes of antigen plus antigen-specific IgE, to protease allergens, or to helminth parasites in vitro and in vivo through the production of "early IL-4" and the presentation to CD4(+) T cells of complexes of peptide plus MHC class II molecules. These findings have uncovered previously unknown functional characteristics of basophils. Knowledge of these and other functional properties of basophils may translate into the design of novel therapeutic strategies for Th2-IgE-mediated diseases, such as bronchial asthma. In this unit, protocols that will enable the study of mouse basophils are described.

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Basophils Play a Critical Role in the Development of IgE-Mediated Chronic Allergic Inflammation Independently of T Cells and Mast Cells

Cited by 288 publications

References 51 publications

IgE-activated basophils regulate eosinophil tissue entry by modulating endothelial function

IgE-activated basophils regulate eosinophil tissue entry by modulating endothelial function

FcεRI, but Not FcγR, Signals Induce Prostaglandin D2 and E2 Production from Basophils

Generation and Characterization of Mouse Basophils from Bone Marrow and Purification of Basophils from Spleen

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