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Th17-Associated Cytokines as a Therapeutic Target for Steroid-Insensitive Asthma.

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Steroid-insensitive asthma is an infrequent but problematic airway disease that presents with persistent symptoms, airflow limitation, or recurrent exacerbations even when treated with steroid-based therapies. Because of unsatisfactory results obtained from currently available therapies for steroid-insensitive asthma, a better understanding of its pathogenesis and the development of new targeted molecular therapies are warranted.

Recent studies indicated that levels of interleukin (IL)-17 are increased and both eosinophils and neutrophils infiltrate the airways of severe asthmatics. IL-17 is a proinflammatory cytokine mainly secreted from helper T (Th) 17 cells and is important for the induction of neutrophil recruitment and migration at sites of inflammation.

This review focuses on the pathogenetic role of Th17 cells and their associated cytokines in steroid-insensitive asthma and discusses the prospects of novel therapeutic options targeting the Th17 signaling pathway.

Th17 Cells in Immunity and Autoimmunity.

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Th17 and IL-17 play important roles in the clearance of extracellular bacterial and fungal infections. However, strong evidence also implicates the Th17 lineage in several autoimmune disorders including multiple sclerosis, psoriasis, rheumatoid arthritis, inflammatory bowel disease, systemic lupus erythematosus, and asthma. The Th17 subset has also been connected with type I diabetes, although whether it plays a role in the pathogenicity of or protection from the disease remains a controversial issue.

In this review we have provided a comprehensive overview of Th17 pathogenicity and function, including novel evidence for a protective role of Th17 cells in conjunction with the microbiota gut flora in T1D onset and progression.

Failure in Asthma Control: Reasons and Consequences.

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Clinical research showed that asthma control is an achievable target. However, real-life observations suggest that a significant proportion of patients suffer from symptoms and report lifestyle limitations with a considerable burden on patient's quality of life.

The achievement of asthma control is the result of the interaction among different variables concerning the disease pattern and patients' and physicians' knowledge and behaviour. The failure in asthma control can be considered as the result of the complex interaction among different variables, such as the role of guidelines diffusion and implementation, some disease-related factors (i.e., the presence of common comorbidities in asthma such as gastroesophageal reflux disease (GERD), sleep disturbances and obstructive sleep apnea (OSA), and rhinitis) or patient-related factors (i.e., adherence to treatment, alexithymia, and coping strategies).

Asthma control may be reached through a tailored treatment plan taking into account the complexity of factors that contribute to achieve and maintain this objective.

Dendritic cells in asthma.

The lungs are constantly exposed to antigens, most of which are non-pathogenic and do not require the induction of an immune response.

Dendritic cells (DCs) are situated at the basolateral site of the lungs and continuously scan the environment to detect the presence of pathogens and subsequently initiate an immune response. They are a heterogeneous population of antigen-presenting cells that exert specific functions. Compelling evidence is now provided that DCs are both sufficient and necessary to induce allergic responses against several inhaled harmless allergens. How various DC subsets exactly contribute to the induction of allergic asthma is currently a subject of intense investigation.

We here review the current progress in this field.

The Role of Vitamin D in Chronic Obstructive Pulmonary Disease, Asthma and Other Respiratory Diseases.

The Role of Vitamin D in Chronic Obstructive Pulmonary Disease, Asthma and Other Respiratory Diseases.

Arch Bronconeumol. 2014 Jan 18;

Authors: García de Tena J, El Hachem Debek A, Hernández Gutiérrez C, Izquierdo Alonso JL

Abstract
There has been growing interest in recent years in the extraosseous effects of vitamin D. In this article, we review the physiology of vitaminD, the physiopathological effects associated with vitaminD deficit and the available evidence on its etiopathogenic role in respiratory diseases. Given the pleiotropic actions of vitaminD, it is biologically plausible that the deficit of this vitamin could play a pathogenic role of in the development of various respiratory diseases. However, the many epidemiological studies that have shown an association between low vitaminD levels and a higher risk of developing various respiratory diseases or a poorer prognosis if they do appear, were unable to show causality. Post-hoc analyses of some clinical trials, particularly in chronic obstructive pulmonary disease (COPD) and asthma, appear to suggest that some patient subtypes may benefit from correction of a vitaminD deficit. In this respect, it would be interesting to determine if the interindividual differences found in the effect of vitaminD deficit and responses to correcting this deficit could be explained by the genetic variants involved in vitaminD metabolism. Ultimately, only appropriately designed clinical trials will determine whether 25-OHD supplements can prevent or improve the course of the various respiratory diseases in which an epidemiological association between prognosis and vitaminD deficit has been described.

PMID: 24447429 [PubMed - as supplied by publisher]

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