دورية أكاديمية
أعرض في EDS

Humanized mouse model of skin inflammation is characterized by disturbed keratinocyte differentiation and influx of IL-17A producing T cells.

التفاصيل البيبلوغرافية
العنوان: Humanized mouse model of skin inflammation is characterized by disturbed keratinocyte differentiation and influx of IL-17A producing T cells.
المؤلفون: de Oliveira VL; Laboratory of Medical Immunology, Department of Laboratory Medicine, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands., Keijsers RR, van de Kerkhof PC, Seyger MM, Fasse E, Svensson L, Latta M, Norsgaard H, Labuda T, Hupkens P, van Erp PE, Joosten I, Koenen HJ
المصدر: PloS one [PLoS One] 2012; Vol. 7 (10), pp. e45509. Date of Electronic Publication: 2012 Oct 19.
نوع المنشور: Journal Article; Research Support, Non-U.S. Gov't
اللغة: English
بيانات الدورية: Publisher: Public Library of Science Country of Publication: United States NLM ID: 101285081 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1932-6203 (Electronic) Linking ISSN: 19326203 NLM ISO Abbreviation: PLoS One Subsets: MEDLINE
أسماء مطبوعة: Original Publication: San Francisco, CA : Public Library of Science
مواضيع طبية MeSH: Disease Models, Animal* , Skin Transplantation*, Inflammation/*immunology , Interleukin-17/*biosynthesis , Keratinocytes/*immunology , Skin/*immunology, Animals ; Antigens, Differentiation, T-Lymphocyte/genetics ; Antigens, Differentiation, T-Lymphocyte/immunology ; CD4-Positive T-Lymphocytes/immunology ; CD4-Positive T-Lymphocytes/pathology ; CD4-Positive T-Lymphocytes/transplantation ; CD8-Positive T-Lymphocytes/immunology ; CD8-Positive T-Lymphocytes/pathology ; CD8-Positive T-Lymphocytes/transplantation ; Cell Differentiation ; Cyclosporine/pharmacology ; Elafin/genetics ; Elafin/immunology ; Gene Expression Regulation/drug effects ; Gene Expression Regulation/immunology ; Humans ; Inflammation/drug therapy ; Inflammation/pathology ; Injections, Intraperitoneal ; Interleukin-17/immunology ; Keratinocytes/drug effects ; Keratinocytes/pathology ; Keratins/genetics ; Keratins/immunology ; Ki-67 Antigen/genetics ; Ki-67 Antigen/immunology ; L-Selectin/genetics ; L-Selectin/immunology ; Membrane Glycoproteins/genetics ; Membrane Glycoproteins/immunology ; Mice ; Mice, SCID ; Sirolimus/pharmacology ; Skin/drug effects ; Skin/pathology ; Transplantation, Heterologous ; beta-Defensins/genetics ; beta-Defensins/immunology
مستخلص: Humanized mouse models offer a challenging possibility to study human cell function in vivo. In the huPBL-SCID-huSkin allograft model human skin is transplanted onto immunodeficient mice and allowed to heal. Thereafter allogeneic human peripheral blood mononuclear cells are infused intra peritoneally to induce T cell mediated inflammation and microvessel destruction of the human skin. This model has great potential for in vivo study of human immune cells in (skin) inflammatory processes and for preclinical screening of systemically administered immunomodulating agents. Here we studied the inflammatory skin response of human keratinocytes and human T cells and the concomitant systemic human T cell response.As new findings in the inflamed human skin of the huPBL-SCID-huSkin model we here identified: 1. Parameters of dermal pathology that enable precise quantification of the local skin inflammatory response exemplified by acanthosis, increased expression of human β-defensin-2, Elafin, K16, Ki67 and reduced expression of K10 by microscopy and immunohistochemistry. 2. Induction of human cytokines and chemokines using quantitative real-time PCR. 3. Influx of inflammation associated IL-17A-producing human CD4+ and CD8+ T cells as well as immunoregulatory CD4+Foxp3+ cells using immunohistochemistry and -fluorescence, suggesting that active immune regulation is taking place locally in the inflamed skin. 4. Systemic responses that revealed activated and proliferating human CD4+ and CD8+ T cells that acquired homing marker expression of CD62L and CLA. Finally, we demonstrated the value of the newly identified parameters by showing significant changes upon systemic treatment with the T cell inhibitory agents cyclosporine-A and rapamycin. In summary, here we equipped the huPBL-SCID-huSkin humanized mouse model with relevant tools not only to quantify the inflammatory dermal response, but also to monitor the peripheral immune status. This combined approach will gain our understanding of the dermal immunopathology in humans and benefit the development of novel therapeutics for controlling inflammatory skin diseases.
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المشرفين على المادة: 0 (Antigens, Differentiation, T-Lymphocyte)
0 (CTAGE1 protein, human)
0 (DEFB4A protein, human)
0 (Elafin)
0 (IL17A protein, human)
0 (Interleukin-17)
0 (Ki-67 Antigen)
0 (Membrane Glycoproteins)
0 (PI3 protein, human)
0 (beta-Defensins)
126880-86-2 (L-Selectin)
68238-35-7 (Keratins)
83HN0GTJ6D (Cyclosporine)
W36ZG6FT64 (Sirolimus)
تواريخ الأحداث: Date Created: 20121025 Date Completed: 20130401 Latest Revision: 20211021
رمز التحديث: 20231215
مُعرف محوري في PubMed: PMC3477148
DOI: 10.1371/journal.pone.0045509
PMID: 23094018
قاعدة البيانات: MEDLINE
الوصف
تدمد:1932-6203
DOI:10.1371/journal.pone.0045509