Aberrant epidermal expression of semaphorin 3A and nerve growth factor in prurigo nodularis

Takada, Shinnosuke; Kou, Kenzen; Nagashima, Yoji; Ikezawa, Zenrō; Aihara, Michiko

doi:10.1111/1346-8138.12085

Cited by 9 publications

(8 citation statements)

References 4 publications

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“…These findings could be explained by the results of immunohistochemical staining, which showed enhanced expression of amphiregulin and NGF (factors promoting elongation of nerve fibers) and reduced expression of semaphorin 3A (an inhibitor of neurite outgrowth) in the epidermis at peripheral lesions, whereas central lesions showed the opposite expression patterns. These features were somewhat similar to those of a prior finding of increased NGF and decreased semaphorin 3A expression in the epidermis in human prurigo lesions (33). Nevertheless, intriguingly, scratching was not necessary for the induction of inflammation, because inhibition of scratching by the introduc- tion of an Elizabethan collar did not affect ear swelling responses (Supplemental Fig.…”

Section: Scratching Behavior and Sprouting Of Nerve Fibers In Prurigosupporting

confidence: 87%

“…In addition, it was intriguing to note that intraepidermal nerve fiber sprouting was most marked at the periphery, rather than at the center, of nodules. In human prurigo lesions, contradictory results were reported regarding nerve fiber innervation in the epidermis (33,44). These inconsistent results may be explained by the present mouse model demonstrating transitional changes in the intraepidermal nerve fiber density within lesions.…”

Section: Discussionmentioning

confidence: 59%

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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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Section: Scratching Behavior and Sprouting Of Nerve Fibers In Prurigosupporting

confidence: 87%

Section: Discussionmentioning

confidence: 59%

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

Hashimoto

Satoh

Yokozeki

2015

The Journal of Immunology

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“…The present data indicated that IL‐31 seems to be one of the major pruritogenic factors in scabies lesions. Although intraepidermal sprouting of nerve fibers has been implicated in chronic pruritus, IENFD was enhanced not only in scabies, but also in tick bite lesions that were not pruritic. Thus, intraepidermal nerve fiber sprouting may not be an important factor in scabies pruritus.…”

Section: Discussionmentioning

confidence: 99%

Pruritus in ordinary scabies: IL‐31 from macrophages induced by overexpression of thymic stromal lymphopoietin and periostin

Hashimoto

Satoh

Yokozeki

2019

Allergy

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Abbreviations: Ab, antibody; AD, atopic dermatitis; Ag, antigen; Arg1, arginase 1; CCR4, C-C chemokine receptor type 4; CD, cluster of differentiation; CXCR3, C-X-C chemokine receptor type 3; ELISA, enzyme-linked immunosorbent assay; IENFD, intraepidermal nerve fiber density; Ig, immunoglobulin; IL, interleukin; IL-7Rα, IL-7 receptor α; iNOS, inducible nitric oxide synthase; OSMRβ, oncostatin M receptor β; PAR-2, protease-activated receptor 2; PGP9.5, protein gene product 9.5; pM, peritoneal macrophages; TARC, thymus and activationregulated chemokine; TSLP, thymic stromal lymphopoietin; TSLPR, thymic stromal lymphopoietin receptor. Abstract Background: Scabies is a common contagious skin disease caused by an infestation of the skin by Sarcoptes scabiei var. hominis. A hallmark symptom of scabies is severe itch. Methods: We sought to determine the generation of a pruritogenic cytokine, interleukin (IL)-31, together with immune profiles in skin lesions of ordinary scabies through immunohistochemical and immunofluorescent studies. To elucidate the pathological mechanisms of IL-31 generation, murine peritoneal macrophages were stimulated with various T helper 2 (Th2) cytokines and proteins ex vivo. Results: A large number of CCR4(+) Th2 cells, eosinophils, and basophils infiltrated in scabies lesions. Increased generation of IL-31, thymic stromal lymphopoietin (TSLP), and periostin was also observed. A major population of IL-31(+) cells were Arginase-1(+)/CD163(+) M2 macrophages. Murine peritoneal macrophages showed an M2 phenotype and generated IL-31 when stimulated with TSLP and periostin.Conclusion: IL-31 appeared to be largely generated by M2 macrophages in ordinary scabies lesions. This IL-31 induction was mediated by TSLP and periostin. K E Y W O R D SIL-31, macrophage, periostin, scabies, thymic stromal lymphopoietin

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“…Recent findings suggest a neuropathic involvement in prurigo nodularis, with alterations of C‐fibres, which are unmyelinated nerve fibres that conduct itch . This hyperinnervation in epidermis induces itch hypersensitivity and scratching behaviour, resulting in keratinocyte activation . Although hyperinnervation in epidermis is observed in AD even without prurigo nodularis, a relationship between hyperinnervation and Th2 activation has not been reported.…”

Section: Discussionmentioning

confidence: 99%

Periostin levels correlate with disease severity and chronicity in patients with atopic dermatitis

et al. 2014

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Aberrant epidermal expression of semaphorin 3A and nerve growth factor in prurigo nodularis

Cited by 9 publications

References 4 publications

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

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

Pruritus in ordinary scabies: IL‐31 from macrophages induced by overexpression of thymic stromal lymphopoietin and periostin

Periostin levels correlate with disease severity and chronicity in patients with atopic dermatitis

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