Long-term inhibition of protease hypersensitivity by initial immunological cross-regulation and epigenetic memory in lung stromal cells - PubMed
4 hours ago
- #inflammation
- #lung stromal cells
- #immunological memory
- Prevention and regulation of excessive inflammation is crucial for protecting against inflammatory pathologies like autoimmunity and allergy.
- In a mouse model of acute lung protease hypersensitivity, immunological cross-regulation was used to mitigate pathogenic inflammation.
- Induction of a type 1 response using Toll-like receptor ligands or a bacterial lysate effectively blocks acute eosinophilia and type 2 responses caused by the cysteine protease papain.
- Upon rechallenge with papain weeks later, mice showed enhanced type 2 responses and eosinophilia, unless the initial inflammation was cross-regulated.
- Memory of the initial inflammatory event was stored in adventitial stromal cells expressing CCL11.
- Accessibility of the Ccl11 locus was increased by papain exposure in an interleukin-4- and interleukin-13-dependent manner and blocked by interferon gamma.
- The study demonstrates how the nature of initial inflammation is memorized by tissue-resident cells and influences subsequent inflammatory responses.