Long noncoding RNA lncKdm2b is required for ILC3 maintenance by initiation of Zfp292 expression.
Innate lymphoid cells (ILCs) communicate with other hematopoietic and nonhematopoietic cells to regulate immunity, inflammation and tissue homeostasis. How ILC lineages develop and are maintained remains largely unknown. In this study we observed that a divergent long noncoding RNA (lncRNA), lncKdm2b, was expressed at high levels in intestinal group 3 ILCs (ILC3s). LncKdm2b deficiency in the hematopoietic system led to reductions in the number and effector functions of ILC3s. LncKdm2b expression sustained the maintenance of ILC3s by promoting their proliferation through activation of the transcription factor Zfp292. Mechanistically, lncKdm2b recruited the chromatin organizer Satb1 and the nuclear remodeling factor (NURF) complex onto the Zfp292 promoter to initiate its transcription. Deletion of Zfp292 or Bptf also abrogated the maintenance of ILC3s, leading to susceptibility to bacterial infection. Therefore, our findings reveal that lncRNAs may represent an additional layer of regulation of ILC development and function.
Key Laboratory of Infection and Immunity of CAS, CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China.|University of Chinese Academy of Sciences, Beijing, China.
Benyu
B
Liu
Key Laboratory of Infection and Immunity of CAS, CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China.
Buqing
B
Ye
Key Laboratory of Infection and Immunity of CAS, CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China.|University of Chinese Academy of Sciences, Beijing, China.
Liuliu
L
Yang
Key Laboratory of RNA Biology of CAS, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China.
Xiaoxiao
X
Zhu
Key Laboratory of Infection and Immunity of CAS, CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China.|University of Chinese Academy of Sciences, Beijing, China.
Guanling
G
Huang
Key Laboratory of Infection and Immunity of CAS, CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China.
Pingping
P
Zhu
Key Laboratory of Infection and Immunity of CAS, CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China.
Ying
Y
Du
Key Laboratory of Infection and Immunity of CAS, CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China.|University of Chinese Academy of Sciences, Beijing, China.
Jiayi
J
Wu
Key Laboratory of Infection and Immunity of CAS, CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China.|University of Chinese Academy of Sciences, Beijing, China.
Xiwen
X
Qin
University of Chinese Academy of Sciences, Beijing, China.|Key Laboratory of RNA Biology of CAS, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China.
Runsheng
R
Chen
University of Chinese Academy of Sciences, Beijing, China.|Key Laboratory of RNA Biology of CAS, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China.
Yong
Y
Tian
Key Laboratory of Infection and Immunity of CAS, CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China.|University of Chinese Academy of Sciences, Beijing, China.
Zusen
Z
Fan
D000818:Animals; D034961:Antigens, Nuclear / Q000235:genetics; D001424:Bacterial Infections / Q000235:genetics*; D002454:Cell Differentiation / Q000235:genetics; D019070:Cell Lineage / Q000235:genetics; D049109:Cell Proliferation / Q000235:genetics; D042002:Chromatin Assembly and Disassembly; D004268:DNA-Binding Proteins / Q000235:genetics; D004198:Disease Susceptibility; D044783:F-Box Proteins / Q000235:genetics*; D007113:Immunity, Innate; D056484:Jumonji Domain-Containing Histone Demethylases / Q000235:genetics*; D008214:Lymphocytes / Q000502:physiology*; D036961:Matrix Attachment Region Binding Proteins / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009419:Nerve Tissue Proteins / Q000235:genetics; D062085:RNA, Long Noncoding / Q000235:genetics*; D014157:Transcription Factors / Q000235:genetics; D015533:Transcriptional Activation; D000092468:Bromodomain Containing Proteins
D034961:Antigens, Nuclear; D004268:DNA-Binding Proteins; D044783:F-Box Proteins; D056484:Jumonji Domain-Containing Histone Demethylases; D036961:Matrix Attachment Region Binding Proteins; D009419:Nerve Tissue Proteins; D062085:RNA, Long Noncoding; D014157:Transcription Factors; C469541:Satb1 protein, mouse; C406423:Zfp292 protein, mouse; C406238:fetal Alzheimer antigen; D000092468:Bromodomain Containing Proteins; C524747:Kdm2b protein, mouse