Tuesday, December 13, 2011

does stress induce allergy?

Here is another example of what I call “right paper wrong journal”. This time we should thank journal Science for not disappointing us.

Type I allergic reaction is characterized by production of antigen-specific IgE. Upon re-encounter with the corresponding antigen, IgE molecules engage receptors on mast cells, eosinophils or basophils that results in release of histamine or other active enzymes. These substances induce smooth muscle contraction, capillary permeability, mucus production, leading to clinical signs of asthma, skin rash, itching, mucosal swelling. It seems that IgE responses are bad. So why we have it? In general, evolutionary explanation for IgE response was its role in defense against intestinal parasites (worms). However, today very diverse set of antigens (for example, some food) could induce IgE response. How they do it is not at all clear.

The study I was referring to earlier was recently published in journal Science (1). This paper by Jessica Strid et al., examined an effect of innate T cell activation on IgE response. This innate T cells, called γδ T cells express NKG2D molecules that recognize tissue stress-induced ligand, Rae-1. By analyzing mice where expression of RAE-1 could be manipulated (on/off), the author showed that if skin application of nominal (neutral) antigen, OVA, was coincided with NKG2D-Rae-1 interaction, this led to allergy-prone OVA-specific IL-13 and IgE production from adaptive immune system. They showed that the imprinting of this allergy-prone responses were reduced in γδ T cell-deficient mice, NKG2D-deficient mice or in mice deficient in only subset of γδ T cell residing in mouse skin. The authors concluded that tissue-stressed induced innate T cell activation promotes allergy-prone IgE adaptive immune response.

This paper is very good paper for journal of immunology, for example. It's main strength is the idea that links environmental toxins (chemical pollutants) to allergy development. It's fundamental weakness is its reliance on IgE or IL-13 production as a sole signature of allergic response. They do not provide any data that would suggest that upon antigen re-encounter, this increase in OVA-specific IgE production, as observed in this study, could induce any clinically relevant sign of allergy. Shortly, this study lacks "science-level" relevance.

I personally find it difficult to believe that tissue-surveillance program through NKG2D-Rae-1 interaction should lead to IgE response. After all, tissue-surveillance program was originally thought to be primarily directed against tumors, where protection is mediated  through IFN-γ pathway, not IL-13/IgE pathway.


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