IL-33 is a member of IL-1 family and requires proteolytic cleavage to form active form. It has already been linked to allergy manifestation. Now, new study in nature immunology expands on earlier observations to show that full-length non-active IL-33 (IL-33FL) is a natural target of group of allergens with proteases activity.
In general, many known allergens display protease activity such as from fungi, mites, pollens, insects. Co-incubation of IL-33FL with such allergen proteases in presence of innate lymphoid cells type II (ILC2) generated biologically-active smaller fragments and release of type II cytokines.
IL-33FL is an intra-nuclear proto-chemokine found in epithelial and endothelial cells. So, how allergens get access to it? It requires cell damage to release IL-33FL extra-cellularly. However, it is not clear if any allergen proteases can damage cells. At least one such allergen from fungus, Alternaria alternata (A. alternata) can damage cell and then cleave IL-33FL.
Similar effects were seen in vivo using IL-33KO mice. In these mice, recruitment of eosinophils, a readout for IL-33-driven allergic response, were only observed when injected with pre-incubated IL-33FL and A. alternata mixture.
In summary, these results suggest that allergen from A. alternata with protease activity can damage cells to release IL-33FL and cleave it into biologically-active shorter peptides. However, this study did not show that other allergens can deliver similar double punch. Also, it is not clear how this innate mechanism translates to adaptive immune system to generate allergen-specific T cell and antibody responses.
posted by David Usharauli
IL-33FL is an intra-nuclear proto-chemokine found in epithelial and endothelial cells. So, how allergens get access to it? It requires cell damage to release IL-33FL extra-cellularly. However, it is not clear if any allergen proteases can damage cells. At least one such allergen from fungus, Alternaria alternata (A. alternata) can damage cell and then cleave IL-33FL.
Similar effects were seen in vivo using IL-33KO mice. In these mice, recruitment of eosinophils, a readout for IL-33-driven allergic response, were only observed when injected with pre-incubated IL-33FL and A. alternata mixture.
In summary, these results suggest that allergen from A. alternata with protease activity can damage cells to release IL-33FL and cleave it into biologically-active shorter peptides. However, this study did not show that other allergens can deliver similar double punch. Also, it is not clear how this innate mechanism translates to adaptive immune system to generate allergen-specific T cell and antibody responses.
posted by David Usharauli
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