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1.
Curr Top Microbiol Immunol ; 351: 25-76, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-21833835

RESUMO

Dendritic cells (DC) are the key initiators and regulators of any immune response which determine the outcome of CD4(+) and CD8(+) T-cell responses. Multiple distinct DC subsets can be distinguished by location, phenotype, and function in the homeostatic and inflamed human skin. The function of steady-state cutaneous DCs or recruited inflammatory DCs is influenced by the surrounding cellular and extracellular skin microenvironment. The skin is an attractive site for vaccination given the extended local network of DCs and the easy access to the skin-draining lymph nodes to generate effector T cells and immunoglobulin-producing B cells for long-term protective immunity. In the context of intradermal vaccination we describe in this review the skin-associated immune system, the characteristics of the different skin DC subsets, the mechanism of antigen uptake and presentation, and how the properties of DCs can be manipulated. This knowledge is critical for the development of intradermal vaccine strategies and supports the concept of intradermal vaccination as a superior route to the conventional intramuscular or subcutaneous methods.


Assuntos
Imunidade Adaptativa , Infecções Bacterianas/prevenção & controle , Imunidade Inata , Células de Langerhans , Pele/imunologia , Vacinação/métodos , Viroses/prevenção & controle , Adjuvantes Imunológicos/administração & dosagem , Animais , Apresentação de Antígeno/imunologia , Antígenos CD/imunologia , Infecções Bacterianas/imunologia , Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD8-Positivos/imunologia , Diferenciação Celular/imunologia , Linhagem da Célula/imunologia , Movimento Celular/imunologia , Proliferação de Células , Homeostase/imunologia , Humanos , Injeções Intradérmicas , Células de Langerhans/citologia , Células de Langerhans/imunologia , Macrófagos/imunologia , Camundongos , Pele/anatomia & histologia , Vacinas/administração & dosagem , Vacinas/imunologia , Viroses/imunologia
2.
Exp Dermatol ; 18(3): 212-7, 2009 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-19046297

RESUMO

Polymorphic light eruption (PLE) is a putative delayed-type allergic reaction to (solar) ultraviolet (UV) exposure. Inadequate immune suppression after UVB-induced sunburn appears to be associated with reduced trafficking of Langerhans cells (LCs) out of and neutrophils into the epidermis of patients sensitive to UVB provocation of PLE. Therefore, we investigated whether pro-inflammatory and chemotactic cytokines are differentially expressed in UVB-irradiated skin of UVB-provocable PLE patients (n = 6) and age- and gender-matched healthy controls (n = 6). Interstitial interleukin-1alpha (IL-1alpha), IL-1beta, IL-1Ra, IL-4, IL-8, tumor necrosis factor-alpha (TNF-alpha), macrophage inflammatory protein 1-alpha (MIP-1alpha), MIP-1beta and monocyte chemotactic protein-1 (MCP-1) were measured in suction blister fluid raised 16 h after exposure to 0, three and six minimal erythemal UVB doses. In unirradiated skin, the IL-1Ra levels were significantly lower in the PLE patients than in controls (P < 0.05). IL-8 and TNF-alpha levels increased strongly upon UVB irradiation in both groups. No differential shifts in cytokine profiles were found that could explain a reduced trafficking of Langerhans cells and neutrophils in PLE patients. Dose-trend analyses showed that UVB irradiation caused significant increases in IL-1alpha in both groups, and that the levels of IL-1alpha and IL-1beta were on average twofold higher in the PLE group (P = 0.03 and P = 0.004, respectively.). Accordingly, the ratios of IL-1Ra over IL-1alpha and over IL-1beta were overall lower in the skin of PLE patients (P = 0.015 and P < 0.001, respectively.). This shift in cytokines in UVB-irradiated skin of PLE patients reveals an amplified early pro-inflammatory cytokine response, which may contribute to the allergic reaction to UVB radiation.


Assuntos
Proteína Antagonista do Receptor de Interleucina 1/metabolismo , Interleucina-1/metabolismo , Transtornos de Fotossensibilidade/metabolismo , Pele/metabolismo , Pele/efeitos da radiação , Raios Ultravioleta , Adulto , Estudos de Casos e Controles , Movimento Celular/efeitos da radiação , Feminino , Humanos , Interleucina-1alfa/metabolismo , Interleucina-1beta/metabolismo , Interleucina-8/metabolismo , Células de Langerhans/patologia , Células de Langerhans/efeitos da radiação , Masculino , Pessoa de Meia-Idade , Neutrófilos/patologia , Neutrófilos/efeitos da radiação , Transtornos de Fotossensibilidade/patologia , Fator de Necrose Tumoral alfa/metabolismo
3.
Br J Dermatol ; 154(2): 361-4, 2006 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-16433811

RESUMO

BACKGROUND: Lichen planus (LP) is a common inflammatory skin disease of unknown aetiology. Viral causes have been suggested. OBJECTIVES: To find candidate viruses associated with LP. METHODS: Lesional and nonlesional skin samples, peripheral blood mononuclear cells and serum were obtained from patients with LP. Ultrastructural, viral DNA, immunohistochemical and serological analyses were performed, and comparisons were made with psoriatic and normal skin. RESULTS: Electron microscopy revealed typical 120-200-nm enveloped particles with a 100-nm nucleus resembling human herpesvirus (HHV) virions both in dermis and in epidermis of lesional LP tissue. HHV-7 DNA was found in 11 of 18 lesional LP samples, as opposed to only one of 11 nonlesional LP samples (P =0.06), two of 11 lesional psoriasis samples (P = 0.05) and none of four normal skin samples. No relation was found between LP skin and DNA of other known HHVs (HHV-1-6 and 8). With immunohistochemistry, significantly more HHV-7+ cells were found in lesional LP epidermis than in normal epidermis. Lesional LP dermis contained significantly more HHV-7+ cells than nonlesional LP, psoriatic or normal dermis. Moreover, LP skin contained overwhelmingly and consistently more plasmacytoid dendritic cells (upregulated in virally induced conditions) than nonlesional LP samples. CONCLUSIONS: We conclude that HHV-7 replicates in LP lesions, but not in psoriasis, another inflammatory skin condition. HHV-7 is possibly involved in the pathogenesis of LP. These preliminary data make further research on this topic of interest.


Assuntos
Células Dendríticas/patologia , Herpesvirus Humano 7/isolamento & purificação , Líquen Plano/virologia , Adulto , Herpesvirus Humano 7/fisiologia , Herpesvirus Humano 7/ultraestrutura , Humanos , Líquen Plano/imunologia , Líquen Plano/patologia , Microscopia Eletrônica , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase/métodos , Psoríase/imunologia , Psoríase/virologia , Pele/ultraestrutura , Pele/virologia , Replicação Viral
4.
Br J Dermatol ; 152(6): 1098-107, 2005 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-15948970

RESUMO

The current understanding of the function of natural killer (NK) T cells in innate immunity and their potential to control acquired specific immunity, as well as the remarkable efficacy of antitumour necrosis factor-alpha biological treatments in psoriasis, forces us to refine the current T-cell hypothesis of psoriasis pathogenesis, and to give credit to the role of innate immunity. Psoriasis might be envisioned to be a genetically determined triggered state of otherwise dormant innate immunity. This aggravated state of innate immunity is represented by the activity of NK T cells, dendritic cells, neutrophils and keratinocytes, leading to the recruitment and activation of preferentially type 1 T cells, possibly in an antigen-independent way. Keratinocytes in psoriasis then are sensitive to the effects of T-cell activation and cytokine production, interferon (IFN)-gamma, by responding with psoriasiform hyperplasia. The chronic inflammation of psoriatic lesions suggests that this might be due to a deficiency in downregulation processes (e.g. a defect in the regulatory T-cell repertoire) and/or the persistence of an unknown trigger resulting in an exaggerated innate immune response.


Assuntos
Antígenos/imunologia , Imunidade Inata , Queratinócitos/imunologia , Células Matadoras Naturais/imunologia , Modelos Imunológicos , Psoríase/imunologia , Células Dendríticas/imunologia , Predisposição Genética para Doença , Humanos , Memória Imunológica , Ativação Linfocitária , Polimorfismo Genético , Psoríase/genética , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/imunologia
5.
Exp Dermatol ; 13(12): 764-72, 2004 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-15560760

RESUMO

Type-1 cytokine-producing T cells are important in the pathogenesis of psoriasis vulgaris, for which efficient therapy is provided by means of narrow-band ultraviolet-B (NB-UVB). The expression of the type-1 cytokine interferon-gamma (IFN-gamma) is regulated by interleukin-12 (IL-12), IL-15, IL-18 and IL-23; however, not much is known about the effect of this therapy on the levels of these cytokines in lesional psoriatic skin in situ. In this study, we investigated the effects of NB-UVB therapy on the expression of IFN-gamma-inducing cytokines. Ten patients with chronic plaque-type psoriasis selected to be treated with NB-UVB therapy were recruited for these experiments and the expression of cytokines IL-12, IL-15, IL-18, IL-23 and IFN-gamma in lesional psoriatic skin before, during and after therapy was determined with the help of immunohistochemistry. Double staining was performed in order to determine the cell types expressing these cytokines. The decrease in the psoriasis area and severity index was accompanied by a significant decrease in the expression of IFN-gamma, and concomitantly, significant reduction of IFN-gamma inducers -- IL-12, IL-18 and IL-23. Thus, we concluded that the decrease of IFN-gamma expression in psoriasis lesions after NB-UVB therapy could be a result of diminished expression of IL-12, IL-18 and IL-23 in lesional skin. Therapies targeting these three cytokines should, therefore, be considered in the treatment of psoriasis.


Assuntos
Interferon gama/metabolismo , Interleucina-12/biossíntese , Interleucina-18/biossíntese , Interleucinas/biossíntese , Psoríase/metabolismo , Psoríase/radioterapia , Raios Ultravioleta , Adulto , Feminino , Humanos , Imuno-Histoquímica , Interleucina-23 , Subunidade p19 da Interleucina-23 , Masculino , Pessoa de Meia-Idade
6.
Ann Rheum Dis ; 63(7): 769-73, 2004 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-15194570

RESUMO

BACKGROUND: Tumour necrosis factor alpha (TNFalpha) blockade using infliximab, a chimeric anti-TNFalpha antibody, is an effective treatment for both psoriasis and psoriatic arthritis (PsA). OBJECTIVE: To analyse the early effects of infliximab treatment on serial skin and synovial tissue biopsy samples. METHODS: Twelve patients with both active psoriasis and PsA received a single infusion of either infliximab (3 mg/kg) (n = 6) or placebo (n = 6) intravenously. Synovial tissue and lesional skin biopsy specimens were obtained at baseline and 48 hours after treatment. Immunohistochemical analysis was performed to analyse the inflammatory infiltrate. In situ detection of apoptotic cells was performed by TUNEL assay and by immunohistochemical staining with anti-caspase-3 antibodies. Stained tissue sections were evaluated by digital image analysis. RESULTS: A significant reduction in mean (SEM) T cell numbers was found in both lesional epidermis (baseline 37 (11) cells/mm, 48 hours 26 (11), p = 0.028) and synovial tissue (67 (56) cells/mm(2)v 32 (30), p = 0.043) after infliximab treatment, but not after placebo treatment (epidermis 18 (8) v 43 (20), NS; synovium 110 (62) v 46 (21), NS). Similarly, the number of macrophages in the synovial sublining was significantly reduced after anti-TNFalpha treatment (100 (73) v 10 (8), p = 0.043). The changes in cell numbers could not be explained by induction of apoptosis at the site of inflammation. CONCLUSIONS: The effects of anti-TNFalpha therapy in psoriasis and psoriatic arthritis may be explained by decreased cell infiltration in lesional skin and inflamed synovial tissue early after initiation of treatment.


Assuntos
Anticorpos Monoclonais/uso terapêutico , Artrite Psoriásica/tratamento farmacológico , Psoríase/tratamento farmacológico , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Adulto , Idoso , Apoptose , Artrite Psoriásica/imunologia , Artrite Psoriásica/patologia , Método Duplo-Cego , Feminino , Humanos , Imuno-Histoquímica , Marcação In Situ das Extremidades Cortadas , Infliximab , Contagem de Linfócitos , Macrófagos/imunologia , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Psoríase/imunologia , Psoríase/patologia , Pele/imunologia , Pele/patologia , Membrana Sinovial/imunologia , Membrana Sinovial/patologia , Linfócitos T/imunologia , Fatores de Tempo , Fator de Necrose Tumoral alfa/imunologia
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