WASH maintains NKp46+ ILC3 cells by promoting AHR expression

Pengyan Xia; Jing Liu; Shuo Wang; Buqing Ye; Ying Du; Zhen Xiong; Ze-Guang Han; Liang Tong; Zusen Fan

doi:10.1038/ncomms15685

WASH maintains NKp46⁺ ILC3 cells by promoting AHR expression

Nat Commun. 2017 Jun 7:8:15685. doi: 10.1038/ncomms15685.

Authors

Pengyan Xia¹, Jing Liu^{1

2}, Shuo Wang¹, Buqing Ye¹, Ying Du¹, Zhen Xiong^{1

2}, Ze-Guang Han³, Liang Tong⁴, Zusen Fan^{1

2}

Affiliations

¹ Key Laboratory of Infection and Immunity of CAS, CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China.
² University of Chinese Academy of Sciences, Beijing 100049, China.
³ Key Laboratory of Systems Biomedicine (Ministry of Education) and Collaborative Innovation Center of Systems Biomedicine, Shanghai Center for Systems Biomedicine, Shanghai Jiao Tong University, Shanghai 200240, China.
⁴ Department of Biological Sciences, Columbia University, New York, New York 10027, USA.

Abstract

Innate lymphoid cells (ILCs) communicate with other haematopoietic and non-haematopoietic cells to regulate immunity, inflammation and tissue homeostasis. How these ILC lineages develop and are maintained is not clear. Here we show that WASH is highly expressed in the nucleus of group 3 ILCs (ILC3s). WASH deletion impairs the cell pool of NKp46⁺ ILC3s. In NKp46⁺ ILC3s, WASH recruits Arid1a to the Ahr promoter thus activating AHR expression. WASH deletion in ILC3s decreases the number of NKp46⁺ ILC3s. Moreover, Arid1a deletion impedes AHR expression and impairs the maintenance of NKp46⁺ ILC3s. Therefore, WASH-mediated AHR expression has a critical function in the maintenance of NKp46⁺ ILC3s.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Antigens, Ly / metabolism
Bone Marrow Cells / metabolism
Bone Marrow Transplantation
Cell Line, Tumor
DNA-Binding Proteins / metabolism
Female
Gene Deletion
Green Fluorescent Proteins / metabolism
Hematopoietic Stem Cells / metabolism
Humans
Immunity, Innate*
In Situ Hybridization, Fluorescence
Inflammation / metabolism*
Lymphocytes / metabolism*
Mice
Mice, Inbred C57BL
Microfilament Proteins / metabolism*
Natural Cytotoxicity Triggering Receptor 1 / metabolism*
Nuclear Proteins / metabolism*
Protein Domains
Transcription Factors / metabolism*
Vesicular Transport Proteins / metabolism

Substances

ARID1A protein, human
Antigens, Ly
Arid1a protein, mouse
DNA-Binding Proteins
Microfilament Proteins
NCR1 protein, human
Natural Cytotoxicity Triggering Receptor 1
Ncr1 protein, mouse
Nuclear Proteins
Transcription Factors
Vesicular Transport Proteins
WASH protein, human
WASH protein, mouse
Green Fluorescent Proteins