Non-Histaminergic Itch Mediators Elevated in the Skin of a Porcine Model of Scabies and of Human Scabies Patients

Sanders, Kristen M.; Nattkemper, Leigh; Rosen, Jordan; Andersen, Hjalte Holm; Hsiang, J.; Romanelli, Paolo; Bernigaud, C.; Guillot, Jacques; Chosidow, Olivier; Yosipovitch, Gil

doi:10.1016/j.jid.2018.09.032

Cited by 31 publications

(36 citation statements)

References 13 publications

(11 reference statements)

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“…Thus, intraepidermal nerve fiber sprouting may not be an important factor in scabies pruritus. Similarly, it seemed unlikely that mast cells largely contributed to itching, as an increase in mast cells was not observed in scabies lesions …”

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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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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“…The number of dermal infiltrating cells was manually quantified. The IENF density was calculated by dividing the number of neuron specific marker b-tubulin III(þ) nerves crossing the dermo-epidermal junction by the length of the epidermis (Sanders et al, 2019).…”

Section: Quantificationmentioning

confidence: 99%

Mechanisms of Itch in Stasis Dermatitis: Significant Role of IL-31 from Macrophages

Hashimoto

Kursewicz

Fayne

et al. 2020

Journal of Investigative Dermatology

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Stasis dermatitis (SD) is a common disease in the elderly population, with pruritus being one of the troublesome symptoms. However, there are few therapeutic modalities available for SD-associated itch because little is known about its pathophysiological mechanism. Therefore, we sought to investigate the mediators of itch in SD using an immunofluorescence study on patient lesions focusing on IL-31. Ex vivo stimulation studies using murine peritoneal macrophages were also used to elucidate the pathological mechanisms of the generation of IL-31. In SD lesions, dermal infiltrating IL-31(þ) cells were increased in number compared with the healthy controls, and the majority of IL-31(þ) cells were CD68(þ) macrophages. The presence of itch in SD was significantly associated with the amount of CD68(þ)/IL-31(þ) macrophages and CD68(þ)/CD163(þ) M2 macrophages. The number of CD68(þ)/IL-31(þ) macrophages was correlated with the number of dermal CC chemokine receptor type 4(þ) T helper type 2 cells, IL-17(þ) cells, basophils, substance P(þ) cells, and dermal deposition of periostin and hemosiderin. Furthermore, murine peritoneal macrophages expressed an M2 marker arginase-1 and generated IL-31 when stimulated with a combination of substance P, periostin, and red blood cell lysate (representing hemosiderin). IL-31 from macrophages may play a role in itch in SD.

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“…Upon damage or stress, keratinocytes (KCs) and skin microbiota emit cytokines, AMPs, and proteases that activate immunocytes and nerves [38,40,41]. Protease-activated receptors (PARs), which are cleaved by serine proteases, manifest on different cell types, including sensory neurons and mediate itch [42][43][44][45]. β-defensin, an AMP released from epithelial cells, has the ability to stimulate IL-31 production by mast cells [46].…”

Section: The Skin Microbiota the Skin Barrier And Itchmentioning

confidence: 99%

The Skin Microbiota and Itch: Is There a Link?

Kim

Yosipovitch

2020

JCM

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Itch is an unpleasant sensation that emanates primarily from the skin. The chemical mediators that drive neuronal activity originate from a complex interaction between keratinocytes, inflammatory cells, nerve endings and the skin microbiota, relaying itch signals to the brain. Stress also exacerbates itch via the skin–brain axis. Recently, the microbiota has surfaced as a major player to regulate this axis, notably during stress settings aroused by actual or perceived homeostatic challenge. The routes of communication between the microbiota and brain are slowly being unraveled and involve neurochemicals (i.e., acetylcholine, histamine, catecholamines, corticotropin) that originate from the microbiota itself. By focusing on itch biology and by referring to the more established field of pain research, this review examines the possible means by which the skin microbiota contributes to itch.

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Non-Histaminergic Itch Mediators Elevated in the Skin of a Porcine Model of Scabies and of Human Scabies Patients

Cited by 31 publications

References 13 publications

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

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

Mechanisms of Itch in Stasis Dermatitis: Significant Role of IL-31 from Macrophages

The Skin Microbiota and Itch: Is There a Link?

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