Review Articles in 2012

This review describes how the evolving field of neuroepigenetics can provide a new understanding of the mechanisms involved in neurodevelopmental and neurodegenerative disorders. It also discusses how epigenetic therapeutics that have been approved for other diseases, such as cancer, could be useful in modulating neurological conditions associated with epigenetic abnormalities.

Fibrosis is a key aspect of many chronic inflammatory diseases and can affect almost every tissue in the body. This review discusses recent advances in our understanding of the mechanisms of fibrosis, focusing on the innate and adaptive immune responses. It also describes how some of these crucial pathogenic pathways are being therapeutically targeted in the clinic.

Genomic technologies are being rapidly applied to the area of prenatal diagnosis, and many genomic prenatal tests have already been transitioned to the clinic. Diana Bianchi reviews these advances in prentatal diagnosis and highlights the challenges in bringing them to the clinic. She also discusses how genomic and transcriptomic technologies might be applied to understand the pathology of fetal diseases and disorders of pregnancy and, perhaps, develop new therapies for these conditions.

This review outlines recent advances in the development of therapeutics that induce immune tolerance to treat asthma and allergic disease. It focuses on the distinct approaches of allergen-specific immunotherapy and biological immune modifiers and also highlights the possibility of combining these two strategies to harness the advantages of both types of therapy and address current unmet clinical needs associated with these conditions.

Efficient trafficking of lymphocytes between the blood, lymphoid organs and peripheral tissues is essential for an effective immune response. Sabina Islam and Andrew Luster summarize recent findings on the regulation of leukocyte homing to the lungs, gut and skin in allergic inflammation and how leukocyte trafficking can be targeted clinically.

Allergen sensitization is triggered by activating receptors of the innate arm of the immune system. This leads to the recruitment and activation of dendritic cells, which have a sentinel role in orchestrating the attendant adaptive response. Stephen Holgate highlights recent findings on how innate receptors are triggered, cellular sources of cytokines driving immune cell activation and the identification of new helper T cell subsets driving chronic allergic airway inflammation.

Viral infections can worsen episodes of allergic sensitization to allergens, putting the affected individuals, often children, at risk for developing persistent asthma during adult life. Understanding how the mechanisms mediating the antiviral response and driving allergic inflammation caused by allergens interact is crucial. This will provide insights into when and what player or molecule to target for treatment and prevention of asthma in children at the early stages of the disease.

The airway epithelium has a sentinel role in initiating allergic responses and asthma. Bart Lambrecht and Hamida Hammad review recent findings on how allergens activate epithelial cells and induce the production of cytokines and chemokines that recruit and activate dendritic cells and other cells of the innate immune system. Activation of these cell types promotes adaptive immune responses, which are, the authors argue, further maintained and perpetuated by their interaction with airway epithelial cells.

The growing appreciation of asthma as a heterogeneous disease has led to the concept that asthma consists of multiple, different phenotypes, but now the challenge is to link underlying biology to phenotypes to allow a more robust classification and understanding of asthma. This review discusses the progress in defining asthma phenotypes and provides insights into how to apply this knowledge to provide more personalized approaches to treating asthma.

Both mast cells and IgE play crucial parts during the initiation and amplification of the allergic response during asthma, as well as during the tissue remodeling that occurs at the chronic stage. This review discusses how these two players can affect the development of asthma through independent and interdependent functions and the therapeutic implications for treating the clinical symptoms derived from allergic disease.

This review highlights the importance of immunometabolism to obesity and metabolic diseases such as diabetes. The authors describe recent advances in dissecting the cellular and signaling networks that link the immune and metabolic systems together, and how these insights could be translated to develop new therapeutic strategies to combat metabolic disease.