Mouse Models of Psoriasis

Slides:



Advertisements
Similar presentations
Figure 1 Simplified scheme of TGFβ signalling
Advertisements

Topical Application of A Novel Immunomodulatory Peptide, RDP58, Reduces Skin Inflammation in the Phorbol Ester-Induced Dermatitis Model  Christopher G.
Laurent L'homme, PhD, David Dombrowicz, PhD 
Functions of the Peroxisome Proliferator-Activated Receptor (PPAR) α and β in Skin Homeostasis, Epithelial Repair, and Morphogenesis  Guillaume Icre,
Toll-like receptors: Applications to dermatologic disease
Jan-Hendrik B. Hardenberg, Andrea Braun, Michael P. Schön 
Toll-like receptors in Borrelia burgdorferi-induced inflammation
Whipping NF-κB to Submission via GADD45 and MKK7
Tumor necrosis factor: Biology and therapeutic inhibitors
EGFR and IL-1 Signaling Synergistically Promote Keratinocyte Antimicrobial Defenses in a Differentiation-Dependent Manner  Andrew Johnston, Johann E.
Nat. Rev. Rheumatol. doi: /nrrheum
Regulation and Function of the Caspase-1 in an Inflammatory Microenvironment  Dai-Jen Lee, Fei Du, Shih-Wei Chen, Manando Nakasaki, Isha Rana, Vincent.
Keratins and the Keratinocyte Activation Cycle
Andrew Blauvelt, Mark G. Lebwohl, Robert Bissonnette 
Vitali Alexeev, Kyonggeun Yoon  Journal of Investigative Dermatology 
David M. Lonard, Bert W. O'Malley  Molecular Cell 
Volume 142, Issue 4, Pages (August 2010)
David M. Lonard, Bert W. O'Malley  Molecular Cell 
The Role of Smads in Skin Development
Pseudomonas Aeruginosa- and IL-1β-Mediated Induction of Human β-Defensin-2 in Keratinocytes Is Controlled by NF-κB and AP-1  Kai Wehkamp, Lars Schwichtenberg,
Keratinocyte Apoptosis in Epidermal Development and Disease
Keratinocyte–Fibroblast Interactions in Wound Healing
A New Twist in Smad Signaling
Jo-Ellen Murphy, Caroline Robert, Thomas S. Kupper 
A Dynamic Model of Keratinocyte Stem Cell Renewal and Differentiation: Role of the p21WAF1/Cip1 and Notch1 Signaling Pathways  Ryuhei Okuyama, Karine.
Epithelial Cells Promote Fibroblast Activation via IL-1α in Systemic Sclerosis  Nima Aden, Anna Nuttall, Xu Shiwen, Patricia de Winter, Andrew Leask, Carol.
Connecting Mitochondria and Innate Immunity
Characterization of the Progressive Skin Disease and Inflammatory Cell Infiltrate in Mice with Inhibited NF-κB Signaling  Max van Hogerlinden, Barbro.
Outside-in Signaling through Integrins and Cadherins: A Central Mechanism to Control Epidermal Growth and Differentiation?  Eliane J. Müller, Lina Williamson,
Molecular Dissection of Psoriasis: Integrating Genetics and Biology
Tissue Regeneration: Hair Follicle as a Model
Lack of Evidence for Activation of the Hedgehog Pathway in Psoriasis
Histamine Enhances the Production of Granulocyte-Macrophage Colony-Stimulating Factor via Protein Kinase Cα and Extracellular Signal-Regulated Kinase.
Figure 2 A model of TNFR–complex I signalling
All-Trans-Retinoic Acid Induces Interleukin-8 via the Nuclear Factor-κB and p38 Mitogen-Activated Protein Kinase Pathways in Normal Human Keratinocytes 
Molecular Mechanisms Regulating Hair Follicle Development
Proteins Kinases: Chromatin-Associated Enzymes?
The Suppressor of Cytokine Signaling (SOCS)-3 Determines Keratinocyte Proliferative and Migratory Potential during Skin Repair  Andreas Linke, Itamar.
Functional Diversity and Regulation of Different Interleukin-1 Receptor-Associated Kinase (IRAK) Family Members  Sophie Janssens, Rudi Beyaert  Molecular.
SRC and STAT Pathways Journal of Thoracic Oncology
Volume 123, Issue 6, Pages (December 2002)
Evidence for Altered Wnt Signaling in Psoriatic Skin
The Nf1 Tumor Suppressor Regulates Mouse Skin Wound Healing, Fibroblast Proliferation, and Collagen Deposited by Fibroblasts  Radhika P. Atit, Maria J.
YAP and TAZ Regulate Skin Wound Healing
Volume 19, Issue 5, Pages (September 2005)
Schematic summary of the mechanisms by which tick-borne Phlebovirus NSs proteins inhibit the canonical IFN induction and signaling pathways. Schematic.
Survivin: A Dual Player in Healthy and Diseased Skin
NF-κB activation in pathogenesis and therapy of cancer.
Erik G. Huntzicker, Anthony E. Oro 
Manabu Taniguchi, Shinsuke Matsuzaki, Masaya Tohyama 
Genetic Control of MHC Class II Expression
Dual-Mode Regulation of Hair Growth Cycle by Two Fgf-5 Gene Products
TGFβ Signaling in Growth Control, Cancer, and Heritable Disorders
Normal Wound Healing in Mice Deficient for Fibulin-5, an Elastin Binding Protein Essential for Dermal Elastic Fiber Assembly  Qian Zheng, Jiwon Choi,
Organization of Stem Cells and Their Progeny in Human Epidermis
NF-κB/Rel/IκB: Implications in gastrointestinal diseases
Alexander Kiani, Anjana Rao, Jose Aramburu  Immunity 
Volume 73, Issue 6, Pages (March 2008)
TAK1 Is Required for Dermal Wound Healing and Homeostasis
A Wnt Survival Guide: From Flies to Human Disease
Vladimir A. Botchkarev  Journal of Investigative Dermatology 
Functional Diversity and Regulation of Different Interleukin-1 Receptor-Associated Kinase (IRAK) Family Members  Sophie Janssens, Rudi Beyaert  Molecular.
Loss of Keratin 10 Leads to Mitogen-activated Protein Kinase (MAPK) Activation, Increased Keratinocyte Turnover, and Decreased Tumor Formation in Mice 
Sorting Out the p63 Signaling Network
Cross-regulation of Signaling Pathways by Interferon-γ: Implications for Immune Responses and Autoimmune Diseases  Xiaoyu Hu, Lionel B. Ivashkiv  Immunity 
Akane Tanaka, Susumu Muto, Kyungsook Jung, Akiko Itai, Hiroshi Matsuda 
Keratinocyte-Derived Granulocyte-Macrophage Colony Stimulating Factor Accelerates Wound Healing: Stimulation of Keratinocyte Proliferation, Granulation.
Volume 7, Issue 1, Pages 1-11 (July 1997)
Characterization of the MM.1 human multiple myeloma (MM) cell lines
The Regulatory T Cell Transcriptosome: E Pluribus Unum
Presentation transcript:

Mouse Models of Psoriasis Johann E. Gudjonsson, Andrew Johnston, Melissa Dyson, Helgi Valdimarsson, James T. Elder  Journal of Investigative Dermatology  Volume 127, Issue 6, Pages 1292-1308 (June 2007) DOI: 10.1038/sj.jid.5700807 Copyright © 2007 The Society for Investigative Dermatology, Inc Terms and Conditions

Figure 1 Histological comparison of normal human (a, d), mouse skin (b, e) and human-mouse xenograft (c, f). The figure shows a 0.4-mm-thick human skin xenograft 42 days after transplantation into a NOD/LtSz-Prkdcscid/Prkdcscid recipient, and serves to illustrate some of the differences in the anatomy of human versus mouse skin described in the text. Note that no human follicles are visible in the xenograft shown, which was derived from a keratome biopsy of buttocks skin. Mouse epidermis generally comprises only three cell layers and is <25μm in thickness, whereas human epidermis commonly constitutes 6–10 cell layers and is >50μm thick. It is also noteworthy that the short inter-follicular regions in mouse skin do not contain any rete ridges. Human dermis is substantially thicker than mouse dermis and contains fewer hair follicles. Finally, mice contain an entire cutaneous muscle layer, the panniculus carnosus. Journal of Investigative Dermatology 2007 127, 1292-1308DOI: (10.1038/sj.jid.5700807) Copyright © 2007 The Society for Investigative Dermatology, Inc Terms and Conditions

Figure 2 Summary of various mouse models and their resemblance to human psoriasis – modified and expanded from Xia et al. (2003). The first row indicates the characteristic changes seen in human psoriasis (Y, yes; N; no). Other models are compared with the human standard and are blocked in green if they match human psoriasis or in red if they do not match. Question marks and the yellow blocks indicate that the feature in question was not examined. It is noteworthy that several models have most of the listed features of psoriasis, although several of the features seen in the mice, like elongation of rete ridges, are not as marked as in the human disease and are often difficult to evaluate given the increased density of hair follicles in mice. Given these similarities, it is remarkable that only the xenograft models have so far been successfully used to investigate novel therapeutic agents. Further details of the models based on **appear in Table S1 (transgenics) and 2b (targeted mutations). Xg: xenograft, Alg: MHC-mismatched allograft, and Sp: spontaneous mouse models. Journal of Investigative Dermatology 2007 127, 1292-1308DOI: (10.1038/sj.jid.5700807) Copyright © 2007 The Society for Investigative Dermatology, Inc Terms and Conditions

Figure 3 Some of the biochemical pathways manipulated in transgenic mouse models of psoriasis: STAT3, AP-1 and the NF-κB pathways. (a) Extracellular components that activate STAT pathways include granulocyte colony stimulating factor (G-CSF) (Kamezaki et al., 2005), leptin (Goren et al., 2003), IL-6 (Sriuranpong et al., 2003), and IL-20 (Blumberg et al., 2001). Stat3 is activated through phosphorylation, followed by dimerization and nuclear translocation (Levy and Darnell, 2002). (b) The Jun proteins (Jun, JunB, and JunD), together with the Fos proteins (Fos, FosB, Fra1, and Fra2) and some members of the ATF and CREB protein families are the principal components of the AP-1 transcription factor family (Jochum et al., 2001). Jun plays an essential role in cell proliferation by influencing a number of cell cycle regulators such as p53 and cyclin D1, whereas JunB negatively regulates cell growth by activating the p16INK4a inhibitor and decreasing cyclin D1 expression (Weitzman, 2001). The balance of Jun proteins, with their opposing effects, has been proposed to determine whether cells progress through the cell cycle or die (Weitzman, 2001). Both Jun and JunB knockout mice have an embryonic lethal phenotype (Szabowski et al., 2000). (c) A multitude of extracellular signals are transduced to the nucleus via NF-κB and, crucially, these are controlled by the IκB kinase (IKK) complex. IKK is activated by phosphorylation of its IKKα and IKKβ subunits. IKK is then able to phosphorylate IκB, leading to its dissociation, ubiquitination, and destruction by the proteasome. Once liberated, the active NF-κB dimer (p50 and Rel-A(p65)) enters the nucleus and induces gene transcription. IKKα may also form homodimers, which are activated by NF-κB-inducing kinase (NIK) and lead to gene transcription by NF-κB2 (p52-Rel-B). Journal of Investigative Dermatology 2007 127, 1292-1308DOI: (10.1038/sj.jid.5700807) Copyright © 2007 The Society for Investigative Dermatology, Inc Terms and Conditions

Figure 4 Some of the biochemical pathways manipulated in transgenic mouse models of psoriasis: TGF-β signaling and integrin pathways. (a) TGF-β1 is secreted in a latent form, which after release of a latency-associated peptide, signals via a heterodimeric receptor complex consisting of one of seven type I receptors (TGF-βRI, or activin receptor-like kinases, ALK) and a type II receptor (TGF-βRII). On binding a ligand, the type II receptor recruits and phosphorylates the type I receptors, which activate the downstream signaling mediators Smads 2, 3, and 4 (Kretzschmar and Massague, 1998). Interestingly, the known target genes for TGF-β1 are members of the AP-1 family (Wach et al., 2001) (Jonk et al., 1998; Ueyama et al., 1998; Choi et al., 1999; Hollnagel et al., 1999). (b) Each integrin is a heterodimer of an α and a β subunit, which determine the ligand-binding specificity (Hynes, 1992, 2002). β1 integrins are expressed throughout the proliferative compartment of the epidermis (Bata-Csorgo et al., 1993). In healthy intact epidermis, β1 is restricted to the basal layer; however, suprabasal integrin expression (spinous and granular layer, GL) is a feature of hyperproliferative epidermis as found in wound closure (Grose et al., 2002), psoriasis (Pellegrini et al., 1992), and neoplastic keratinocyte disorders (Bagutti et al., 1998). Journal of Investigative Dermatology 2007 127, 1292-1308DOI: (10.1038/sj.jid.5700807) Copyright © 2007 The Society for Investigative Dermatology, Inc Terms and Conditions