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Flutter B.,Kings College London | Nestle F.O.,Kings College London | Nestle F.O.,KCL Comprehensive Biomedical Research Center
European Journal of Immunology | Year: 2013

Psoriasis is an inflammatory disease of the skin affecting 2-3% of the population, characterized by a thickening of the epidermis and immune infiltrates throughout the dermis and epidermis, causing skin lesions that can seriously affect quality of life. The study of psoriasis has historically been hampered by the lack of good animal models. Various genetically induced models exist, which have provided some information about possible mechanisms of disease, but these models rely mostly on intrinsic imbalances of homeostasis. However, a mouse model of psoriasiform dermatitis caused by the repeated topical application of Aldara™ containing 5% imiquimod was described in 2009. The mechanisms of action of Aldara™ are complex. Imiquimod is an effective ligand for TLR7 (and TLR8 in humans) and also interferes with adenosine receptor signaling. In addition, isostearic acid present in the Aldara™ vehicle has been shown to be biologically active and of importance for activating the inflammasome. Interestingly, the repetitive application of Aldara™ reveals a complex aetiology involving multiple cell types, cytokines, and inflammatory pathways. In this review, we will dissect the findings of the imiquimod model to date and ask how this model can inform us about the immunological aspects of human disease. © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim. Source


Villanova F.,Kings College London | Villanova F.,KCL Comprehensive Biomedical Research Center | Flutter B.,Kings College London | Tosi I.,Kings College London | And 13 more authors.
Journal of Investigative Dermatology | Year: 2014

Innate lymphoid cells (ILCs) are increasingly appreciated as key regulators of tissue immunity. However, their role in human tissue homeostasis and disease remains to be fully elucidated. Here we characterize the ILCs in human skin from healthy individuals and from the inflammatory skin disease psoriasis. We show that a substantial proportion of IL-17A and IL-22 producing cells in the skin and blood of normal individuals and psoriasis patients are CD3-negative innate lymphocytes. Deep immunophenotyping of human ILC subsets showed a statistically significant increase in the frequency of circulating NKp44+ ILC3 in the blood of psoriasis patients compared with healthy individuals or atopic dermatitis patients. More than 50% of circulating NKp44+ ILC3 expressed cutaneous lymphocyte-associated antigen, indicating their potential for skin homing. Analysis of skin tissue revealed a significantly increased frequency of total ILCs in the skin compared with blood. Moreover, the frequency of NKp44+ ILC3 was significantly increased in non-lesional psoriatic skin compared with normal skin. A detailed time course of a psoriasis patient treated with anti-tumor necrosis factor showed a close association between therapeutic response, decrease in inflammatory skin lesions, and decrease of circulating NKp44+ ILC3. Overall, data from this initial observational study suggest a potential role for NKp44+ ILC3 in psoriasis pathogenesis. © 2014 The Society for Investigative Dermatology. Source


Villanova F.,Kings College London | Villanova F.,KCL Comprehensive Biomedical Research Center | Di Meglio P.,UK National Institute for Medical Research | Nestle F.O.,Kings College London | Nestle F.O.,KCL Comprehensive Biomedical Research Center
Annals of the Rheumatic Diseases | Year: 2013

Psoriasis is a common immune-mediated disease of the skin, which associates in 20-30% of patients with psoriatic arthritis (PsA). The immunopathogenesis of both conditions is not fully understood as it is the result of a complex interaction between genetic, environmental and immunological factors. At present there is no cure for psoriasis and there are no specific markers that can accurately predict disease progression and therapeutic response. Therefore, biomarkers for disease prognosis and response to treatment are urgently needed to help clinicians with objective indications to improve patient management and outcomes. Although many efforts have been made to identify psoriasis/PsA biomarkers none of them has yet been translated into routine clinical practice. In this review we summarise the different classes of possible biomarkers explored in psoriasis and PsA so far and discuss novel strategies for biomarker discovery. Source


Volponi A.A.,Kings College London | Volponi A.A.,KCL Comprehensive Biomedical Research Center | Sharpe P.T.,Kings College London | Sharpe P.T.,KCL Comprehensive Biomedical Research Center
British Dental Journal | Year: 2013

Mesenchymal stem cells can be obtained with ease from dental/oral tissue, making them an attractive source of autologous stem cells. They offer a biological solution for restoring damaged dental tissues such as vital pulp engineering, regeneration of periodontal ligament lost in periodontal disease, and for generation of complete or partial tooth structures to form biological implants. Dental mesenchymal stem cells share properties with mesenchymal stem cells from bone marrow and there is a considerable potential for these cells to be used in different stem-cell-based therapies, such as bone and muscle regeneration. In addition, their immunosuppressive-immunomodulatory properties make these cells a suitable source for treating immunodisorders like systematic lupus erythematosus. In addition, gingival tissue might also be a very good source of epithelial cells used in the treatment of severe ocular surface disorders. Being such an accessible source for different stem cells, the tooth and the attached gingival tissue (usually discarded in the clinics) represent an ideal source of autologous or allogeneic stem cells that can be used in the treatment of many clinical conditions in dentistry and medicine. © 2013 Macmillan Publishers Limited. Source

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