Keratinocyte-derived CHI3L2 rewires phospholipid metabolism to drive skin inflammation in psoriasis
- CHI3L2, a chitinase-like protein, is raised in serum and lesional skin of psoriasis patients, mainly in keratinocytes, and is induced by inflammatory cytokines.
- Mice expressing human CHI3L2 develop worse psoriasis-like disease in two induction models.
- Parabiosis, bone marrow transplantation and keratinocyte-specific knockin mice point to keratinocytes as the pathogenic source.
- In keratinocytes, CHI3L2 disrupts phospholipid homeostasis, altering inflammatory responses and proliferation.
💡 Points Based on the abstract
Human CHI3L2 knock-in worsening two induced models is gain-of-function evidence only; I'd want knockout or neutralization to show necessity, and psoriasis mouse models are IL-23/imiquimod-driven and notoriously forgiving. CHI3L2 has no known enzymatic activity, so a druggable handle is unclear. Does the phospholipid readout shift in patient skin, and which species?