Reviews & Analysis

A new study shows that melanoma-derived exosomes contribute to metastatic invasion by carrying messenger proteins that direct bone marrow–derived cells toward a prometastatic phenotype. This leads to the promotion of proangiogenic events and modification of the extracellular matrix at premetastatic sites (pages 883–891).

How blood-borne inflammatory cells cause tissue damage in the brain after ischemic stroke remains elusive. Peroxiredoxins, cytosolic antioxidant proteins vital for redox balance, are released extracellularly from ischemic cells, acting as potent 'danger signals' that activate macrophages and lead to a harmful cytokine response, a new study shows. The findings unveil a new culprit in the delayed phase of ischemic injury and suggest new therapeutic approaches (pages 911–917).

Metastatic colorectal cancer is a largely incurable disease with a pressing need for targeted therapies. A new study sheds light on a surprising interaction between FOXO3a and β-catenin in metastatic colorectal cancer, suggesting new therapeutic avenues for agents targeting the PI3K-AKT pathway (pages 892–901).

The link between tobacco use and aneurysms of the abdominal aorta is well established, but the specific mechanisms involved have remained elusive for decades. A new study indicates that nicotine is the major culprit in cigarette smoke and provides a common mechanism of aneurysm formation that may allow the development of drugs to treat this disease, for which currently only surgical treatments exist (pages 902–910).

Bariatric surgery to treat obesity can also be effective against type 2 diabetes, but it is unclear how such surgical procedures improve glucose metabolism. A new study in rats suggests that nutrient sensing in the jejunum contributes to the antidiabetic effects of duodenal-jejeunal bypass (pages 950–955).

Mechanisms triggering methicillin-resistant Staphylococcus aureus (MRSA) epidemics are poorly understood. A recent study provides new evidence that horizontal gene transfer may be the culprit for the emergence of new resistant and virulent MRSA clones.

The normally harmless behavior of bacteria in the intestinal tract is maintained by community structure and the integrity of host defenses. When either or both of these are compromised, a few disgruntled outcasts can cause a riot, taking down the whole neighborhood (pages 799–806).

A new study using a mouse model of lung diseases is the first demonstration in vivo that bone marrow–derived stromal cells can repair tissue injury through the transfer of mitochondria (pages 751–758). This suggests that rescue of injured cells through mitochondrial transfer may be an important process in many diseases.

Clinicians note that bariatric operations can dramatically resolve type 2 diabetes, often before and out of proportion to postoperative weight loss. Now two randomized controlled trials formally show superior results from surgical compared with medical diabetes care, including among only mildly obese patients. The concept of 'metabolic surgery' to treat diabetes has taken a big step forward.

Alternative splicing ensures the expression of functionally diverse proteins from individual genes; however, aberrant mRNA splicing is associated with various conditions, including heart disease. A recent study provides new mechanistic insights into heart failure by showing that a human cardiomyopathy-linked mutation in a cardiac splice factor affects post-transcriptional regulation, causing the expression of anomalous isoforms of a whole network of cardiac proteins (pages 766–773).

Age-related macular degeneration (AMD) is the most common cause of blindness in the elderly. AMD progression is associated with alterations in inflammatory pathways and the immune system. A new study identifies a protective role for inflammasomes in AMD, suggesting that inflammasome activation might be manipulated as a potential therapeutic strategy for this condition (pages 791–798).

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.

Liver injury promotes the outgrowth of cell types that are relatively rare in healthy livers, including progenitors and stromal cells. A new study shows that the type of injury influences the cellular composition of the liver progenitor niche, which then seems to direct the fate of progenitors during regeneration (pages 572–579).