RORα is required for expansion and memory maintenance of ILC1s via a lymph node-liver axis
Ming Cheng,
Jiarui Li,
Jiaxi Song,
Hao Song,
Yawen Chen,
Hao Tang,
Haiming Wei,
Rui Sun,
Zhigang Tian,
Xianwei Wang,
Hui Peng
Affiliations
Ming Cheng
The Institute of Immunology and the Key Laboratory of Immune Response and Immunotherapy, Biomedical Sciences and Health Laboratory of Anhui Province, School of Basic Medical Sciences, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei 230027, China
Jiarui Li
The Institute of Immunology and the Key Laboratory of Immune Response and Immunotherapy, Biomedical Sciences and Health Laboratory of Anhui Province, School of Basic Medical Sciences, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei 230027, China
Jiaxi Song
The Institute of Immunology and the Key Laboratory of Immune Response and Immunotherapy, Biomedical Sciences and Health Laboratory of Anhui Province, School of Basic Medical Sciences, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei 230027, China
Hao Song
The Institute of Immunology and the Key Laboratory of Immune Response and Immunotherapy, Biomedical Sciences and Health Laboratory of Anhui Province, School of Basic Medical Sciences, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei 230027, China
Yawen Chen
The Institute of Immunology and the Key Laboratory of Immune Response and Immunotherapy, Biomedical Sciences and Health Laboratory of Anhui Province, School of Basic Medical Sciences, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei 230027, China
Hao Tang
The Institute of Immunology and the Key Laboratory of Immune Response and Immunotherapy, Biomedical Sciences and Health Laboratory of Anhui Province, School of Basic Medical Sciences, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei 230027, China
Haiming Wei
The Institute of Immunology and the Key Laboratory of Immune Response and Immunotherapy, Biomedical Sciences and Health Laboratory of Anhui Province, School of Basic Medical Sciences, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei 230027, China
Rui Sun
The Institute of Immunology and the Key Laboratory of Immune Response and Immunotherapy, Biomedical Sciences and Health Laboratory of Anhui Province, School of Basic Medical Sciences, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei 230027, China
Zhigang Tian
The Institute of Immunology and the Key Laboratory of Immune Response and Immunotherapy, Biomedical Sciences and Health Laboratory of Anhui Province, School of Basic Medical Sciences, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei 230027, China; Center for Advanced Interdisciplinary Science and Biomedicine of IHM, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei 230027, China; Research Unit of NK Cell Study, Chinese Academy of Medical Sciences, Beijing, China; Corresponding author
Xianwei Wang
The Institute of Immunology and the Key Laboratory of Immune Response and Immunotherapy, Biomedical Sciences and Health Laboratory of Anhui Province, School of Basic Medical Sciences, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei 230027, China; Corresponding author
Hui Peng
The Institute of Immunology and the Key Laboratory of Immune Response and Immunotherapy, Biomedical Sciences and Health Laboratory of Anhui Province, School of Basic Medical Sciences, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei 230027, China; Center for Advanced Interdisciplinary Science and Biomedicine of IHM, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei 230027, China; Corresponding author
Summary: Type 1 innate lymphoid cells (ILC1s) possess adaptive immune features, which confer antigen-specific memory responses against haptens and viruses. However, the transcriptional regulation of memory ILC1 responses is currently not known. We show that retinoic acid receptor-related orphan receptor alpha (RORα) has high expression in memory ILC1s in murine contact hypersensitivity (CHS) models. RORα deficiency diminishes ILC1-mediated CHS responses significantly but has no effect on memory T cell-mediated CHS responses. During sensitization, RORα promotes sensitized-ILC1 expansion by suppressing expression of cell-cycle repressors in draining lymph nodes. RORα programs gene-expression patterns related to cell survival and is required for the long-term maintenance of memory ILC1s in the liver. Our findings reveal RORα to be a key transcriptional factor for sensitized-ILC1 expansion and long-term maintenance of memory ILC1s.
