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Synonyms: H. polygyrus Alarmin Release Inhibitor
Compound class:
Peptide or derivative
Comment: H. polygyrus Alarmin Release Inhibitor (HpARI) is a peptide isolated from the secretions of the parasitic helminth Heligmosomoides polygyrus [1]. It was isolated for its anti-inflammatory activity, predicated by the observation that infection with parasitic worms in humans has protective effects against allergic inflammatory conditions such as asthma. HpARI was found to directly bind active IL-33, thereby disrupting the major cellular pathways that drive the inflammatory response to allergens (via group 2 innate lymphoid cells (ILC2s) and eosinophils for example). In addition HpARI also binds nuclear DNA, and was found to tether IL-33 within cells, limiting its release, to further prevent initiation of type 2 allergic responses.
WormBase Parasite has transcript HPBE_0000813301, which is identical to the transcript for HpARI identified by Osbourn et al. (2017) [1]. The transcript encodes a 251 amino acid protein, the first 16 amino acids of which are predictive of a signal peptide motif. Analysis of its structure indicates the presence of three evolutionarily conserved Complement Control Protein (CPP) modules (a.k.a. Short Consensus Repeats (SCRs) or sushi-domains). |
| Immunopharmacology Comments |
| HpARI, a protein secreted by the parasitic helminth Heligmosomoides polygyrus, was identified as a causal agent responsible for suppressed allergic airway responses observed in humans suffering from worm infections. HpARI interferes with IL-33 signalling to dampen the immune response to allergens. |
