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Papel dos monócitos,células dendríticas CD16+ E mielóides do sangue periférico produtores de quimiocinas no lúpus eritematoso sistémico
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Authors
Abstract(s)
Introdução: O Lúpus Eritematoso Sistémico (LES) é uma doença autoimune crónica
caracterizada por autoanticorpos, formação e deposição de imunocomplexos e vasculite sistémica.
Os doentes com LES exibem numerosas alterações do sistema imune envolvendo as células B,
células T e células apresentadoras de antigénio (APC) como os monócitos e células dendríticas,
resultando numa activação e consequente aumento do processamento e apresentação de
antigénios.
No LES, anormalidades nos monócitos e nas células dendríticas do sangue periférico, têm sido
relatadas, encontrando-se essas alterações relacionadas com a fisiopatologia e actividade da
doença. Estudos recentes descreveram alterações, quer no número destas células no sangue
periférico quer da sua capacidade para produzir citocinas inflamatórias, estado de activação e
expressão de receptores de quimiocinas.
As quimiocinas estão envolvidas na migração, tráfego e quimiotaxia de leucócitos e existe uma
grande evidência que a infiltração de linfócitos T e outros leucócitos nos locais de inflamação tem
um papel importante no LES. Estudos recentes têm mostrado elevadas concentrações séricas das
quimiocinas CCL2 (MCP-1), CCL4 (MIP-1β), CCL5 (RANTES), CXCL9 (MIG) e CXCL10 (IP10) em
doença activa.
Objectivos: Quantificar a expressão génica das quimiocinas inflamatórias IP-10, RANTES, MIG,
MCP-1 e MIP-1β, após separação celular, em Mónocitos, Células Dendríticas (CD) CD16+ e CD
mielóides com vista a esclarecer o papel destas células na fisiopatologia da doença.
Métodos: O estudo incluiu 73 indivíduos, 43 com LES, 18 com LES activo (LESA) e 25 com LES
inactivo (LESI) e 30 controlos saudáveis. A frequência e número absoluto de monócitos e DC foram
determinados por citometria de fluxo. A expressão das quimiocinas IP-10, RANTES, MIG, MCP-1,
MIP-1β foi quantificada por PCR em tempo real.
Resultados: Em monócitos purificados observou-se um aumento da expressão de mRNA de
CCL2, CXCL9 e CXCL10 no grupo de LESA comparado com o grupo de Controlo. Não foram
encontradas diferenças na expressão de mRNA de CCL4 e CCL5 nos grupos em estudo.
Relativamente ao subgrupo de CD, CD14-/lowCD16+ o perfil de expressão de mRNA de CXCL9 e
CXCL10 foi similar ao encontrado em monócitos. Nas CD mielóides não foram encontradas
diferenças estatisticamente significativas relativamente à expressão das quimiocinas CXCL9 e
CXCL10.
Conclusão: O aumento da expressão de mRNA de quimiocinas nos monócitos e nas CD CD14-
/lowCD16+ do sangue periférico em doentes com LES parece estar relacionada com a fisiopatologia
e actividade da doença.
Introduction: Systemic lupus erythematosus (SLE) is a chronic, inflammatory autoimmune disease characterized by autoantibodies, immune complex formation and systemic vasculitis. Patients with SLE exihibit aberrations of the immune system involving B cells, T cells and antigen presenting cells (APC), such as monocytes and dendritic cells, resulting in activation and consequent increase antigen processing and presentation. Abnormalities in monocytes and peripheral blood dendritic cells subsets have been reported in SLE and are related with disease physiology and activity. Recent studies have described changes, both in the number of these cells in peripheral blood or in their ability to produce inflammatory cytokines, activation state and expression of chemokin receptors. Chemokines are involved in the migration and chemotaxis of leukocyte traffic and there is a strong evidence that the infiltration of leukocytes at sites of inflammation plays a major role in SLE. Recent studies have shown elevated serum concentrations of the chemokines CCL2 (MCP-1), CCL4 (MIP- 1β), CCL5 (RANTES), CXCL9 (MIG) and CXCL10 (IP10) in active disease. Aims: Quantify and determine the gene expression of the inflammatory chemokines IP-10, RANTES, MIG, MCP-1, and MIP-1β on purified Monocytes, myeloid Dendritic Cells (DC) and CD16+ DC in order to clarify the role of these cells in the physiology of the disease. Methods: 73 individuals were recruited, 43 with SLE,18 with active disease (ASLE), 25 with inactive disease (ISLE) and 30 healthy individuals were also include as control group (HG). The frequency and absolute number of monocytes and DC populations was determined by flow cytometry. The mRNA expression of chemokines IP-10, RANTES, MIG, MCP-1, MIP-1β in SLE patients was quantified by real time PCR Results:In purified monoytes an increased of CCL2, CXCL9 and CXCL10 mRNA expression was found in ASLE compared to HG, and no differences were found for CCL4 and CCL5. Regarding CD14-CD16+ dendritic cell (DC) subset, the obtanaied profile of mRNA expression was similar to those found on monocytes. On myeloid DC no differences were found regarding chemokines CXCL9 and CXCL10 mRNA expression in the studied groups. Conclusion: Abnormalities in chemokine expression among peripheral blood monocytes and CD16+ dendritic cells in SLE appear to be related to SLE patophysiology and disease activity.
Introduction: Systemic lupus erythematosus (SLE) is a chronic, inflammatory autoimmune disease characterized by autoantibodies, immune complex formation and systemic vasculitis. Patients with SLE exihibit aberrations of the immune system involving B cells, T cells and antigen presenting cells (APC), such as monocytes and dendritic cells, resulting in activation and consequent increase antigen processing and presentation. Abnormalities in monocytes and peripheral blood dendritic cells subsets have been reported in SLE and are related with disease physiology and activity. Recent studies have described changes, both in the number of these cells in peripheral blood or in their ability to produce inflammatory cytokines, activation state and expression of chemokin receptors. Chemokines are involved in the migration and chemotaxis of leukocyte traffic and there is a strong evidence that the infiltration of leukocytes at sites of inflammation plays a major role in SLE. Recent studies have shown elevated serum concentrations of the chemokines CCL2 (MCP-1), CCL4 (MIP- 1β), CCL5 (RANTES), CXCL9 (MIG) and CXCL10 (IP10) in active disease. Aims: Quantify and determine the gene expression of the inflammatory chemokines IP-10, RANTES, MIG, MCP-1, and MIP-1β on purified Monocytes, myeloid Dendritic Cells (DC) and CD16+ DC in order to clarify the role of these cells in the physiology of the disease. Methods: 73 individuals were recruited, 43 with SLE,18 with active disease (ASLE), 25 with inactive disease (ISLE) and 30 healthy individuals were also include as control group (HG). The frequency and absolute number of monocytes and DC populations was determined by flow cytometry. The mRNA expression of chemokines IP-10, RANTES, MIG, MCP-1, MIP-1β in SLE patients was quantified by real time PCR Results:In purified monoytes an increased of CCL2, CXCL9 and CXCL10 mRNA expression was found in ASLE compared to HG, and no differences were found for CCL4 and CCL5. Regarding CD14-CD16+ dendritic cell (DC) subset, the obtanaied profile of mRNA expression was similar to those found on monocytes. On myeloid DC no differences were found regarding chemokines CXCL9 and CXCL10 mRNA expression in the studied groups. Conclusion: Abnormalities in chemokine expression among peripheral blood monocytes and CD16+ dendritic cells in SLE appear to be related to SLE patophysiology and disease activity.
Description
Keywords
Lúpus Eritematoso Sistémico Monócitos Célula dendrítica CD14-/low CD16+ Quimiocinas