| First Author | Taketomi Y | Year | 2024 |
| Journal | Immunity | Volume | 57 |
| Issue | 8 | Pages | 1828-1847.e11 |
| PubMed ID | 39002541 | Mgi Jnum | J:353367 |
| Mgi Id | MGI:7710813 | Doi | 10.1016/j.immuni.2024.06.012 |
| Citation | Taketomi Y, et al. (2024) Lipid-orchestrated paracrine circuit coordinates mast cell maturation and anaphylaxis through functional interaction with fibroblasts. Immunity 57(8):1828-1847.e11 |
| abstractText | Interaction of mast cells (MCs) with fibroblasts is essential for MC maturation within tissue microenvironments, although the underlying mechanism is incompletely understood. Through a phenotypic screening of >30 mouse lines deficient in lipid-related genes, we found that deletion of the lysophosphatidic acid (LPA) receptor LPA(1), like that of the phospholipase PLA2G3, the prostaglandin D(2) (PGD(2)) synthase L-PGDS, or the PGD(2) receptor DP1, impairs MC maturation and thereby anaphylaxis. Mechanistically, MC-secreted PLA2G3 acts on extracellular vesicles (EVs) to supply lysophospholipids, which are converted by fibroblast-derived autotaxin (ATX) to LPA. Fibroblast LPA(1) then integrates multiple pathways required for MC maturation by facilitating integrin-mediated MC-fibroblast adhesion, IL-33-ST2 signaling, L-PGDS-driven PGD(2) generation, and feedforward ATX-LPA(1) amplification. Defective MC maturation resulting from PLA2G3 deficiency is restored by supplementation with LPA(1) agonists or PLA2G3-modified EVs. Thus, the lipid-orchestrated paracrine circuit involving PLA2G3-driven lysophospholipid, eicosanoid, integrin, and cytokine signaling fine-tunes MC-fibroblast communication, ensuring MC maturation. |
