The Editor takes a closer look at some of this month's articles

One of the central questions in allergy is why do only a small proportion of proteins elicit Th2-type immune responses? For many years, it was thought that the answer was probably related to a common structure related to specific IgE epitopes on B cells and T cells. However, no such universal structural motif has been found, and it has become increasingly clear that it is the adjuvant properties of the allergen, in particular those that determine its interaction with the innate immune system, that is the common denominator. The literature to support this concept is impressively summarized by Scheurer and colleagues (pp. 1150–1161) in a state-of-the-art review that details the mechanisms involved. Two pathways appear to be of particular importance. Firstly, interactions between the allergenic protein and the TLR4-MD2-LPS pathway on antigen-presenting cells (which chimes with the known requirement for low-dose LPS to stimulate sensitisation to ovalbumin in animal models), and secondly, the protease activity of some allergens which cause epithelial stimulation and production of ILC-2-generating cytokines such as IL-25 and IL-33. A terrific summary of a fascinating story.

Stephan Scheurer, Masako Toda and Stefan Vieths

A dog. (Photo credit: Lady; Wikimedia Commons).

One of the major advances in the immunology of allergic disease in recent years has been the discovery of a new lineage of innate lymphoid cells that mirrors T-cell subtypes and produces large amounts of the signature cytokines 1. ILC2 cells were originally found in the gut of mice infected with helminthic parasites where they produced large amounts of IL-13 and IL-5. The mechanism by which these cells localize to the gut and other tissues is not clear but may have similarities to the homing of adaptive immune cells using adhesion receptors as addressins. α4β7 expressed under the influence of retinoic acid, the main metabolite of vitamin A, is known to localize T cells to the gut, whereas CLA localizes T cells to the skin. Ruiter et al. (pp. 1214–1225) have investigated whether the same applies to ILC. They demonstrated that retinoic acid has a marked effect on both cytokine release by ILC including ILC-2 cells and enhances expression of α4β7 while downgrading expression of CLA. Moreover, vitamin D inhibits this process demonstrating that a balance between vitamins A and D could have a profound effect on gut immunity.

Bert Ruiter

Retinoic acid acts synergistically with IL-2 to induce cytokine production in human ILCs. [See Figure 1 in B. Ruiter et al. (pp. 1214–1225)].

Peanut allergy is a common and potentially life-threatening condition which affects both children and adults. Challenge tests are the gold standard for diagnosis but apart from being time-consuming also carry a degree of risk. To minimize risk, it would be valuable to know how much peanut is likely to be tolerated before a reaction occurs. This information would also be of value in food labelling. Klemans et al. (pp. 1237–1244) have addressed this problem by working out the doses that elicited symptoms and signs in patients undergoing peanut challenge. The mean eliciting doses (ED) that caused objective features of an allergic reaction in 5% of patients were 2.86 mg in adults and 6.38 mg in children with high specific IgE levels predicting a lower ED. These data will help improve the risk assessment of peanut ingestion for both physicians and those responsible for food labelling.

Rob Klemans

Peanuts (Arachis hypogaea). (Photo credit: Texnik; Wikimedia Commons).