Imunopatogênese da psoríase: revisando conceitos / Reviewing concepts in the immunopathogenesis of psoriasis

O conhecimento sobre a fisiopatogenia da psoríase possibilitou o desenvolvimento de ferramentas terapêuticas que visam ao bloqueio do seu gatilho imunológico. Paralelamente, citocinas como o TNF têm sido reconhecidas como integrantes da etiopatogenia da psoríase e comorbidades a ela relacionadas. Estudos genéticos e epidemiológicos contribuíram efetivamente para as conclusões a que se tem chegado atualmente sobre esta complexa patologia.

Insights into the pathogenesis of psoriasis led to the development of therapeutic tools aimed at blocking its immunological trigger. In parallel, cytokines such as the tumor necrosis factor (TNF) have been recognized as playing a crucial role in the pathogenesis of psoriasis and its associated comorbidities. Genetic and immunological studies have contributed effectively towards establishing the currently held concepts regarding this complex disease.

Graft-versus-Leukemia Effect of Nonmyeloablative Stem Cell Transplantation

Nonmyeloablative stem cell transplantation (NST) is increasingly used with beneficial effects because it can be applied to older patients with hematological malignancies and those with various complications who are not suitable for conventional myeloablative stem cell transplantation (CST). Various conditioning regimens differ in their myeloablative and immunosuppressive intensity. Regardless of the type of conditioning regimen, graft-versus- host disease (GVHD) in NST occurs almost equally in CST, although a slightly delayed development of acute GVHD is observed in NST. Although graft-versus-hematological malignancy effects (i.e., graft-versus-leukemia effect, graft-versus-lymphoma effect, and graft-versus-myeloma effect) also occur in NST, completely eradicating residual malignant cells through allogeneic immune responses is insufficient in cases with rapidly growing disease or uncontrolled progressive disease. Donor lymphocyte infusion (DLI) is sometimes combined to support engraftment and to augment the graft-versus-hematological malignancy effect, such as the graft-versus-leukemia effect. DLI is especially effective for controlling relapse in the chronic phase of chronic myelogenous leukemia, but not so effective against other diseases. Indeed, NST is a beneficial procedure for expanding the opportunity of allogeneic hematopoietic stem cell transplantation to many patients with hematological malignancies. However, a more sophisticated improvement in separating graft-versus-hematological malignancy effects from GVHD is required in the future.

Is pancreas development abnormal in the non-obese diabetic mouse, a spontaneous model of type I diabetes?

Despite extensive genetic and immunological research, the complex etiology and pathogenesis of type I diabetes remains unresolved. During the last few years, our attention has been focused on factors such as abnormalities of islet function and/or microenvironment, that could interact with immune partners in the spontaneous model of the disease, the non-obese diabetic (NOD) mouse. Intriguingly, the first anomalies that we noted in NOD mice, compared to control strains, are already present at birth and consist of 1) higher numbers of paradoxically hyperactive ß cells, assessed by in situ preproinsulin II expression; 2) high percentages of immature islets, representing islet neogenesis related to neonatal BETA-cell hyperactivity and suggestive of in utero BETA-cell stimulation; 3) elevated levels of some types of antigen-presenting cells and FasL+ cells, and 4) abnormalities of extracellular matrix (ECM) protein expression. However, the colocalization in all control mouse strains studied of fibroblast-like cells (anti-TR-7 labeling), some ECM proteins (particularly, fibronectin and collagen I), antigen-presenting cells and a few FasL+ cells at the periphery of islets undergoing neogenesis suggests that remodeling phenomena that normally take place during postnatal pancreas development could be disturbed in NOD mice. These data show that from birth onwards there is an intricate relationship between endocrine and immune events in the NOD mouse. They also suggest that tissue-specific autoimmune reactions could arise from developmental phenomena taking place during fetal life in which ECM-immune cell interaction(s) may play a key role

The low efficiency of dendritic cells and macrophages from mice susceptible to Paracoccidioides brasiliensis in inducing a Th1 response

In the present study we evaluated T cell proliferation and Th lymphokine patterns in response to gp43 from Paracoccidioides brasiliensis presented by isolated dendritic cells from susceptible and resistant mice. T cell proliferation assays showed that dendritic cells from susceptible mice were less efficient than those from resistant mice. The pattern of T cell lymphokines stimulated by dendritic cells was always Th1, although the levels of IL-2 and IFN-gamma were lower in T cell cultures from susceptible mice. To determie whether different antigen-presenting cells such as macrophages and dendritic cells stimulated different concentrations of Th1 lymphokines, the production of IFN-gamma and IL-2 was measured. It was observed that dendritic cells were more efficient than macrophages in stimulating lymphoproliferation in resistant mice. However, no significant difference was observed for IFN-gamma or IL-2 production. When cells from susceptible mice were used, macrophages were more efficient in stimulating lymphoproliferation than dendritic cells, but no difference was observed in the production of Th1 cytokine. Taken together, these results suggest the lower efficiency of dendritic cells and macrophages from B10.A mice in stimulating T cells that secrete Th1 lymphokines in vitro, an effect that may be involved in the progression of the disease in vivo