| First Author | Yagyu H | Year | 2025 |
| Journal | Sci Immunol | Volume | 10 |
| Issue | 112 | Pages | eadp0849 |
| PubMed ID | 41134875 | Mgi Jnum | J:374319 |
| Mgi Id | MGI:8259543 | Doi | 10.1126/sciimmunol.adp0849 |
| Citation | Yagyu H, et al. (2025) Lipolysis-microlipophagy cascade regulated by adipose triglyceride lipase drives pathogenic adaptive type 2 immunity. Sci Immunol 10(112):eadp0849 |
| abstractText | A unique subpopulation of memory T helper 2 (T(H)2) cells expressing the interleukin-33 (IL-33) receptor ST2 drives allergic disease pathogenesis. However, the immunometabolic mechanisms that induce ST2(hi) memory T(H)2 cells remain unclear. We show using a mouse model of chronic allergic airway inflammation that long-chain unsaturated fatty acids (LC-UFAs) accumulate in the inflammatory milieu during chronic airway inflammation. Activated T(H)2 cells take up LC-UFAs, transiently store them in lipid droplets (LDs), and catabolize LDs through lipolysis and microlipophagy. LD catabolism regulated by adipose triglyceride lipase (ATGL) activates peroxisome proliferator-activated receptor gamma (PPARgamma). PPARgamma then binds the Il1rl1 locus encoding ST2 and induces ST2(hi) effector and memory T(H)2 cells. In eosinophilic chronic rhinosinusitis, CD45RO(+) CD4 T cells in nasal polyps exhibit microlipophagy and an accessible IL1RL1 enhancer, indicating that these mechanisms are conserved in humans. Thus, the storage and catabolism of inflammatory milieu-derived LC-UFAs direct pathogenic adaptive type 2 immunity, offering potential therapeutic strategies for persistent allergic inflammation. |
