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NLRP3 negatively regulates Treg differentiation through Kpna2-mediated nuclear translocation.

Authors
  • Park, Su-Ho1
  • Ham, Sunyoung2, 3
  • Lee, Arim1
  • Möller, Andreas2, 3
  • Kim, Tae Sung4
  • 1 Division of Life Science, College of Life Science and Biotechnology, Korea University, 145 Anam-ro, Seongbuk-gu, Seoul 02841, Republic of Korea. , (North Korea)
  • 2 Tumour Microenvironment Laboratory, QIMR Berghofer Medical Research Institute, Brisbane, QLD 4006, Australia. , (Australia)
  • 3 Faculty of Health, School of Biomedical Sciences, Queensland University of Technology, Brisbane, QLD, Australia. , (Australia)
  • 4 Division of Life Science, College of Life Science and Biotechnology, Korea University, 145 Anam-ro, Seongbuk-gu, Seoul 02841, Republic of Korea [email protected] , (North Korea)
Type
Published Article
Journal
Journal of Biological Chemistry
Publisher
American Society for Biochemistry and Molecular Biology
Publication Date
Nov 22, 2019
Volume
294
Issue
47
Pages
17951–17961
Identifiers
DOI: 10.1074/jbc.RA119.010545
PMID: 31597697
Source
Medline
Keywords
Language
English
License
Unknown

Abstract

Naïve CD4+ T cells in the periphery differentiate into regulatory T cells (Tregs) in which Foxp3 is expressed for their suppressive function. NLRP3, a pro-inflammatory molecule, is known to be involved in inflammasome activation associated with several diseases. Recently, the expression of NLRP3 in CD4+ T cells, as well as in myeloid cells, has been described; however, a role of T cell-intrinsic NLRP3 in Treg differentiation remains unknown. Here, we report that NLRP3 impeded the expression of Foxp3 independent of inflammasome activation in Tregs. NLRP3-deficient mice elevate Treg generation in various organs in the de novo pathway. NLRP3 deficiency increased the amount and suppressive activity of Treg populations, whereas NLRP3 overexpression reduced Foxp3 expression and Treg abundance. Importantly, NLRP3 interacted with Kpna2 and translocated to the nucleus from the cytoplasm under Treg-polarizing conditions. Taken together, our results identify a novel role for NLRP3 as a new negative regulator of Treg differentiation, mediated via its interaction with Kpna2 for nuclear translocation. © 2019 Park et al.

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