Papain protease activity and mast cells, but not IL-33, are necessary for papain allergic sensitization

Papain is a proteolytic enzyme from papaya. Like other protease allergens such house dust mites (HDM) group 1 allergen, Der p 1, papain is allergen that belongs to family of cysteine proteases. Papain can induce skin contact sensitization or airway hyper-reactivity. 

New study from Journal of Immunology showed that in mice papain skin allergy and IgE production required intact protease activity and presence of functional mast cells, but not IL-33 (proto-TH2 cytokine).

When injected in mouse ear lobes, intact papain, but not protease-inactive papain (E64-papain), induced skin inflammation and IgE production.

Papain induced IgE production after skin challenge depended on presence of functional mast cells as (a) such response was diminished in mast cell–deficient WBB6F1-W/W^v (W/W^v) mice, and (b) such response could be recovered after transfer of WT mast cells. 

However, unlike mast cells, IL-33 was dispensable for IgE production after papain skin [primary] challenge (though IL-33 played the role in lung eosinophil infiltration later on, upon airway re-challenge with intact papain).

In summary, this study indicate that initial skin sensitization with papain required mast cells but not proto-TH2 innate "primer" cytokine IL-33. This knowledge should be incorporated in therapeutic strategies targeting IL-33 pathway (IL-33 and its receptor ST2).

David Usharauli