Histological and immunocytochemical studies of human psoriatic lesions transplanted onto SCID mice

Sugai, Junichi; Iizuka, Mana; Kawakubo, Yo; Ozawa, A.; Ohkido, Muneo; Ueyama, Y; Tamaoki, Norikazu; Inokuchi, Sadaki; Shimamura, Kazuo

doi:10.1016/s0923-1811(97)00077-7

Cited by 25 publications

(20 citation statements)

References 9 publications

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“…Recent establishment of the SCID-human skin chimeras with transplanted psoriasis plaques has opened new vistas to study the molecular complexities involved in psoriasis (Nickoloff et al, 1995). Histologic and immunologic features of psoriasis can be maintained in the transplanted plaques for more than 3 mo (Gilhar et al, 1997;Sugai et al, 1998) and our experience is that these features are maintained for more than 6 mo. In this study, we have demonstrated that K252a, an inhibitor of signal transductions induced by NGF/NGF-R interaction, is therapeutically effective in psoriasis.…”

Section: Discussionmentioning

confidence: 79%

K252a, a High-Affinity Nerve Growth Factor Receptor Blocker, Improves Psoriasis: An In Vivo Study Using the Severe Combined Immunodeficient Mouse–Human Skin Model

Raychaudhuri¹,

Sanyal²,

Weltman³

et al. 2004

Journal of Investigative Dermatology

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The peripheral nervous system, in addition to its sensory and motor functions, can induce a local inflammatory response known as neurogenic inflammation. This phenomenon plays a critical role in several inflammatory diseases, e.g., asthma, atopy, rheumatoid arthritis, psoriasis, and ulcerative colitis. Neurogenic inflammation and the role of nerve growth factor (NGF) have been extensively studied in psoriasis. There are increased levels of NGF in the keratinocytes and upregulation of NGF receptor (NGF-R) in the cutaneous nerves of psoriatic plaques. NGF can influence all the salient pathologic events noticed in psoriasis such as proliferation of keratinocytes, angiogenesis, T cell activation, expression of adhesion molecules, proliferation of cutaneous nerves, and upregulation of neuropeptides. In this double-blinded, placebo-controlled study, we addressed the role of NGF/NGF-R in psoriasis in an in vivo system using the severe combined immunodeficient (SCID) mouse-human skin model of psoriasis. The transplanted psoriatic plaques on the SCID mice (n=12) were treated with K252a, a high-affinity NGF receptor blocker. Psoriasis significantly improved following 2 wk of therapy. The length of the rete pegs changed from 308.57+/-98.72 to 164.64+/-46.78 microm (p<0.01, Student's t test). A similar improvement of psoriasis was observed by directly inhibiting NGF with NGF-neutralizing antibody. NGF-neutralizing antibody in normal saline at 10 ng (n=4) and 20 ng (n=4) per kilogram of body weight doses were used. Both doses of NGF-neutralizing antibody reduced rete peg lengths significantly, e.g., from 298.5+/-42.69 to 150.52+/-32.93 microm (p<0.05, Student's t test). This study provides evidence for the role of NGF and its high-affinity receptor in the pathogenesis of psoriasis and insights to develop novel therapeutic modalities.

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Section: Discussionmentioning

confidence: 79%

K252a, a High-Affinity Nerve Growth Factor Receptor Blocker, Improves Psoriasis: An In Vivo Study Using the Severe Combined Immunodeficient Mouse–Human Skin Model

Raychaudhuri¹,

Sanyal²,

Weltman³

et al. 2004

Journal of Investigative Dermatology

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“…In fact, single-cell suspensions are rapidly recognized and lysed by mice NK cells (Meyerrose et al, 2003). However, in SCID mice, grafts of solid tissues are well tolerated and psoriatic characteristics are maintained for several months in the transplantations involving psoriatic skin Takizawa et al, 1995 (Sugai et al, 1998). In this latter study, the psoriatic phenotype was well maintained but the histological and immunohistochemical characteristics gradually disappeared as lymphocytic infiltration of the psoriatic lesion declined.…”

Section: Xenotransplantationmentioning

confidence: 70%

“…+ (Hansson, et al, 2002) Xenotransplantation Athymic nude mouse + + ? - (Fraki, et al, 1983;Krueger, et al, 1981) SCID + + + + (Boehncke et al, 1994;Gilhar, et al, 1997;Nickoloff et al, 1995;Sugai, et al, 1998;Takizawa, et al, 1995) AGR129 + + + + (Boyman, et al, 2004) …”

Section: Spontaneous Mutationmentioning

confidence: 99%

In Vivo and In Vitro Models of Psoriasis

Jean¹,

Pouliot²

2010

Tissue Engineering

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“…Moreover, after 22 weeks of grafting, apart from persistence of acanthosis and hyperkeratosis there was resolution of Munro's microabscesses, loss of parakeratosis, and decrease in lymphocytic infiltrates in the transplanted grafts. [64] However, in transplanted grafts, all the pathological features of psoriasis could be maintained longer by intradermal or intravenous administration of T cells derived from psoriatic plaques, but not from peripheral blood mononuclear cells (PBMCs). [64] Interestingly, injection of autologous immunocytes activated with Staphylococcus enterotoxins (SEB and SEC2) and IL-2 into non-lesional skin grafts from psoriatic patients induced immunological as well as histopathological features of psoriasis.…”

Section: Exploring Pathogenesis Of Psoriasismentioning

confidence: 99%

“…[64] However, in transplanted grafts, all the pathological features of psoriasis could be maintained longer by intradermal or intravenous administration of T cells derived from psoriatic plaques, but not from peripheral blood mononuclear cells (PBMCs). [64] Interestingly, injection of autologous immunocytes activated with Staphylococcus enterotoxins (SEB and SEC2) and IL-2 into non-lesional skin grafts from psoriatic patients induced immunological as well as histopathological features of psoriasis. [47,48] In another study, administration of PBMC, stimulated by superantigen (staphylococcal superantigen exfoliative toxin) into non-lesional psoriatic skin resulted in histopathological features of psoriasis as well as infiltrates of CD3 positive cells expressing cutaneous lymphocyte associated antigen.…”

Section: Exploring Pathogenesis Of Psoriasismentioning

confidence: 99%

Severe combined immunodeficiency mouse-psoriatic human skin xenograft model: A modern tool connecting bench to bedside

Kundu-Raychaudhuri

Datta-Mitra

Abria

et al. 2014

Indian J Dermatol Venereol Leprol

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Psoriasis is a multifactorial chronic inflammatory disease. Research into the pathogenesis of this disease is hindered by the lack of a proper animal model. Over the past two decades, many scientists were involved in the development of animal models that nearly mirror the immunopathogenesis of psoriasis. One such model, which has opened doors to the study of molecular complexities of psoriasis as well as its treatment, is the severe combined immunodeficiency (SCID) mouse-human skin chimera model. This model not only mirrors the clinical and histopathological features of psoriasis but also help in the study of cell proliferation, angiogenesis, function of T cells, neurogenic inflammation and cytokines involved in inflammatory reactions. In this article, we have reviewed the prospects and the limitations of the SCID mouse model of psoriasis.

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Histological and immunocytochemical studies of human psoriatic lesions transplanted onto SCID mice

Cited by 25 publications

References 9 publications

K252a, a High-Affinity Nerve Growth Factor Receptor Blocker, Improves Psoriasis: An In Vivo Study Using the Severe Combined Immunodeficient Mouse–Human Skin Model

K252a, a High-Affinity Nerve Growth Factor Receptor Blocker, Improves Psoriasis: An In Vivo Study Using the Severe Combined Immunodeficient Mouse–Human Skin Model

In Vivo and In Vitro Models of Psoriasis

Severe combined immunodeficiency mouse-psoriatic human skin xenograft model: A modern tool connecting bench to bedside

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