CD1d functions as a ligand for PIRA2 to drive macrophage activation in nonalcoholic fatty liver disease
macrophages. Additionally, CD1d and LILRA2 protein levels were elevated in NAFLD patients, and CD1d stimulation induced proinflammatory cytokine expression in human macrophages, which was attenuated by LILRA2 blockade. A recombinant LILRA2/Fc fusion protein effectively blocked CD1d-induced inflammatory gene expression in human macrophages, highlighting its potential as a therapeutic strategy for NAFLD. Collectively, our findings identify CD1d as a functional ligand of PIRA2 that promotes macrophage activation and inflammation, contributing to inflammatory progression in NAFLD.
Authors
- Peixiang Lan (ORCID: https://orcid.org/0000-0001-7569-894X)
- Xiufang Weng (ORCID: https://orcid.org/0000-0003-2625-2137)
- Li Chen (ORCID: https://orcid.org/0000-0002-6989-1177)
- Lingjuan Sun
- Ma Zx
- Xiaosheng Tan (ORCID: https://orcid.org/0000-0001-9920-1555)
- Jingzeng Wang (ORCID: https://orcid.org/0000-0002-3458-0635)
- Xiangli Zhao
- Qi Li (ORCID: https://orcid.org/0000-0001-8776-8730)
- Jianlin Chen (ORCID: https://orcid.org/0000-0003-1172-1148)
- Zhishui Chen
Institutions
- Ministry of Education of the People's Republic of China (CN)
- Chinese Academy of Sciences (CN)
- Chinese Academy of Medical Sciences & Peking Union Medical College (CN)
- Wuhan University (CN)
- Ministry of Education (SA)
- Ministry of Education (KR)
- Laboratoire de Chimie Organique (FR)
- Tongji Hospital (CN)
- Huazhong University of Science and Technology (CN)
Publication Details
- Journal
- Cell Death and Disease
- Published
- 2026-04-27
- DOI
- https://doi.org/10.1038/s41419-026-08789-9
- Primary Topic
- Immune cells in cancer
- Type
- article
- Field-Weighted Citation Impact
- 0.00