Requirement of RORα for maintenance and antitumor immunity of liver‐resident natural killer cells/ILC1s. Issue 5 (6th December 2021)

• Record Type: Journal Article
• Authors: Song, Jiaxi; Song, Hao; Wei, Haiming; Sun, Rui; Tian, Zhigang; Peng, Hui
• Is Part Of: Hepatology. Volume 75:Issue 5(2022)
• Page Start: 1181
• Page End: 1193
• Publication Date: 2021-12-06
• Subjects: Heart -- Diseases -- Nursing -- Periodicals; Lungs -- Diseases -- Nursing -- Periodicals; Intensive care nursing -- Periodicals; Foie -- Maladies -- Périodiques; 616.362
• DOI: 10.1002/hep.32147
• Languages: English
• ISSNs: 0270-9139

Abstract

Abstract: Backgroud and Aims: Liver type 1 innate lymphoid cells (ILC1s), also known as liver‐resident natural killer (LrNK) cells, comprise a high proportion of total hepatic ILCs. However, factors regulating their maintenance and function remain unclear. Approach and Results: In this study, we found high expression of retinoid‐related orphan nuclear receptor alpha (RORα) in LrNK cells/ILC1s. Mice with conditional ablation of retinoid‐related orphan nuclear receptor alpha ( Rorα ) in LrNK cells/ILC1s and conventional natural killer (cNK) cells had decreased LrNK cells/ILC1s but normal numbers of cNK cells. RORα‐deficient LrNK cells/ILC1s displayed increased apoptosis and significantly altered transcriptional profile. Using a murine model of colorectal cancer liver metastasis, we found that RORα conditional deficiency resulted in more aggressive liver tumor progression and impaired effector molecule expression in LrNK cells/ILC1s. Consequently, treatment with the RORα agonist efficiently limited liver metastases and promoted effector molecule expression of LrNK cells/ILC1s. Conclusions: This study reveals a role of RORα in LrNK cell/ILC1 maintenance and function, providing insights into the harnessing of LrNK cell/ILC1 activity in the treatment of liver cancer.