Basophil recruitment and activation in inflammatory skin diseases

Ito, Yatsuji; Satoh, Takahiro; Takayama, Kaoru; Miyagishi, Chiyako; Walls, Andrew F.; Yokozeki, Hiroo

doi:10.1111/j.1398-9995.2011.02570.x

Cited by 239 publications

(260 citation statements)

References 35 publications

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“…45 Most notably, the skin lesions found in these diseases are histologically characterized by a marked basophil infiltration. 46 Thus, basophil-derived PGD2 may at least partly contribute to the pathogenesis of these inflammatory skin reactions.…”

Section: Discussionmentioning

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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Section: Discussionmentioning

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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“…This study also provided evidence that basophils are indispensable key players that link urticarial and papulonodular skin reactions. The fact that a number of basophils are present in long-lasting urticarial lesions and prurigo in humans (15) suggests that basophils, but not mast cells or T cells, play a major role in the pathogenesis of these diseases. One of the major and troublesome symptoms of prurigo is itching.…”

Section: Discussionmentioning

confidence: 99%

“…Prurigo lesions are histopathologically characterized by lymphocyte and eosinophil infiltration, with dermal edema and/or exudates. In addition, our recent findings revealed that prurigo is a disease involving prominent basophil infiltration (15). Basophils principally reside in the blood rather than peripheral tissues.…”

mentioning

confidence: 99%

“…Basophils principally reside in the blood rather than peripheral tissues. However, in some inflammatory conditions, basophils are recruited to the skin (15). Although they share morphological and functional similarities with mast cells, basophils have unique functions; for example, in addition to producing IL-4 and IL-13 (16)(17)(18), they play important roles in acquired immunity against helminths and ticks and in IgGdependent anaphylactic reactions (19)(20)(21).…”

mentioning

confidence: 99%

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Protective Role of STAT6 in Basophil-Dependent Prurigo-like Allergic Skin Inflammation

Hashimoto

Satoh

Yokozeki

2015

The Journal of Immunology

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Prurigo is a common, but treatment-resistant, skin disease characterized by persistent papules/nodules and severe itching. Prurigo occurs in association with various underlying diseases, such as diabetes, chronic renal failure, and internal malignancies. Atopic dermatitis is occasionally complicated by prurigo lesions. However, the pathology of prurigo is completely undefined. We demonstrate that repeated intradermal administration of Ag to IgE-transgenic mice causes persistent and pruritic papulonodular skin lesions mimicking prurigo. Skin lesions were histopathologically characterized by irregular acanthosis and dermal cellular infiltrates comprising eosinophils, mononuclear cells, and basophils, with epidermal nerve fiber sprouting. In vivo depletion of basophils alleviated skin reactions, indicating that the inflammation is basophil dependent. Unexpectedly, STAT6 signaling was unnecessary for skin lesion development if IgE was present. Moreover, the absence of STAT6 signaling exacerbated the inflammation, apparently as the result of impaired generation of an M2-type anti-inflammatory macrophage response. These results provide novel insights into the pathologic mechanisms underlying prurigo. Although basophils are indispensable for prurigo-like inflammation, Th2 immunity mediated by STAT6 appears to play a protective role, and therapies targeting Th2-type cytokines may risk aggravating the inflammation.

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“…A cell type that was brought into focus of allergy research is basophils. Immunohistochemistry using a novel human-specific anti-basogranulin antibody (BB1) revealed basophil infiltration in lesional skin suggesting an active pathogenic role in AD (102).…”

Section: Innate Immune Cells Involved In Admentioning

confidence: 99%

Update in clinical allergy and immunology

Gunten

Marsland

Garnier

et al. 2012

Allergy

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In the recent years, a tremendous body of studies has addressed a broad variety of distinct topics in clinical allergy and immunology. In this update, we discuss selected recent data that provide clinically and pathogenetically relevant insights or identify potential novel targets and strategies for therapy. The role of the microbiome in shaping allergic immune responses and molecular, as well as cellular mechanisms of disease, is discussed separately and in the context of atopic dermatitis, as an allergic model disease. Besides summarizing novel evidence, this update highlights current areas of uncertainties and debates that, as we hope, shall stimulate scientific discussions and research activities in the field.Research progress goes ahead fast, and each issue of Allergy distributes a dozen of new and interesting papers providing actual research results, opinions and reviews in different fields of allergy and clinical immunology. Over time, it becomes difficult to keep an overview on the novelties and trends given by these articles. Here, we give an update aiming to summarize interesting papers published in Allergy over the last years and putting them in context with recently published work in the field. As we were not able to cover all fields, we selected three research subjects: (i) Hygiene hypothesis: the role of the microbiome in allergy; (ii) Pathogenic mechanisms of allergic diseases and their potential therapeutic implications; (iii) Atopic dermatitis (AD): skin barrier and allergic inflammation. In our view, the selected papers provide new insights in clinically and pathogenetically important research as well as novel targets and strategies for therapy that might become starting points for future research.

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Basophil recruitment and activation in inflammatory skin diseases

Abstract: Basophils infiltrate into skin lesions more commonly than previously thought, and thus they may play important roles in a variety of inflammatory skin diseases.

Cited by 239 publications

References 35 publications

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

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

Protective Role of STAT6 in Basophil-Dependent Prurigo-like Allergic Skin Inflammation

Update in clinical allergy and immunology

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