Thursday, November 5, 2015

IL-13/CCL17 axis drives Th2 memory response to allergen

Allergic response is immunological "mystery". In allergy, first step is sensitization when immune system detects new entity [hapten/antigen] and marks it for IgE mediated destruction. This step is more confusing because all kind of bio/chemical entities could be marked for IgE path by immune system, for no apparent reason.

No universal hypothesis exists that could explain and predict allergic response. Right now, we are just left to treat clinical "effector stage" [that usually happens during re-challenge with the same entity].

The following paper from Nature Immunology is one of those type of research articles. Here, the authors showed that memory Th2 response to allergen require engagement of IL-13 producing innate lymphoid cell type 2 (ILC2), followed by CCL17 producing DCs.

The authors used papain allergy model. In this model eosinophils are rapidly recruited in response to papain re-challenge (at day 15).

Next, the authors used gene-modified mouse strain (ICOS-T mouse) where ILC2 could be selectively depleted. Papain re-challenge of ICOS-T mice depleted of ILC2 reduced Th2 accumulation in the lung.
Next, the authors found that IL-13 and CCL17 were rapidly produced in the lung upon papain re-challenge.

They found that ILC2 were primary producers of IL-13 upon papain re-challenge.

They also found that neutralization of either IL-13 or CCL17 reduced Th2 accumulation in the lung upon papain re-challenge.
Next, the authors found that IL-13 receptor expression on DCs were necessary for lung CCL17 production and Th2 accumulation in response to papain re-challenge.

Finally, the authors showed that similar mechanism of Th2 accumulation was operational in papain re-challenged skin as well.

In summary, this study indicates that effector stage of allergic response were promoted by IL-13ILC2 / CCL17DCs axis. This knowledge provides additional therapeutic targets for allergy management.
David Usharauli

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