Monday, October 19, 2015

Food allergies caused by mast cells with a serial number 9

Allergies are complex immune responses. Whether allergic reaction have any "protective" function or represent a purely pathological reaction is still debated. Classical form of allergy is IgE mediated and require IL-4 and Th2 cells. However, the list of effector molecules and cells responsible for various forms of allergic reactions are continuously expanding.

For example, in a recent paper in Immunity the authors showed that certain mouse models of food allergy were driven by mucosal mast cells secreting high level of IL-9.

This is quite messy paper with lots of figures. In fact, it was under review for one year [and it shows by its lack of harmonized relationship between figures]. 

Initially, using mouse model of food sensitization [intra-gastric antigen gavage], the authors showed that allergic reactions (e.g. diarrhea) to antigen in susceptible mouse strains correlated with the number of GI mast cells, not serum IgE. Moreover, such correlation was highly significant for IL-9 producing lamina propria Lin-/- population in susceptible mouse strains [since not every mouse strain develop allergic response in this setting].

Further investigation with IL-4eGFP reporter mice revealed that this IL-9 producing Lin-/- population belonged to mast cell lineage, rather than innate lymphoid cell type 2 (that express IL-25 cytokine receptor IL-17RB).

Next, the authors showed that induction of IL-9+ mast cells (MMC9) required IL-4, STAT6 and T cells.

Finally, using BM chimera experiments the authors showed that while active signaling through IL-9 was dispensable for MMC9 induction, it was required to produce allergic phenotype.


In summary, this study suggests that GI tissue associated mast cell secreting high levels of IL-9 play a role in allergic response to sensitized antigens. The development of this MMC9 requires signaling via IL-4, STAT6 and T cells, implying typical Th2-driven immune response. It is possible [but not formally tested in this study] that therapeutic targeting of IL-9 pathway may benefit patients suffering from GI tract allergies to food.

David Usharauli

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