NLRP3 negatively regulates Treg differentiation through Kpna2-mediated nuclear translocation

Su Ho Park, Sunyoung Ham, Arim Lee, Andreas Möller, Tae Sung Kim

Research output: Contribution to journalArticle

1 Citation (Scopus)

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 Tregpolarizing 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.

Original languageEnglish
Pages (from-to)17951-17961
Number of pages11
JournalJournal of Biological Chemistry
Volume294
Issue number47
DOIs
Publication statusPublished - 2019 Jan 1

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

NLRP3 negatively regulates Treg differentiation through Kpna2-mediated nuclear translocation. / Park, Su Ho; Ham, Sunyoung; Lee, Arim; Möller, Andreas; Kim, Tae Sung.

In: Journal of Biological Chemistry, Vol. 294, No. 47, 01.01.2019, p. 17951-17961.

Research output: Contribution to journalArticle

Park, Su Ho ; Ham, Sunyoung ; Lee, Arim ; Möller, Andreas ; Kim, Tae Sung. / NLRP3 negatively regulates Treg differentiation through Kpna2-mediated nuclear translocation. In: Journal of Biological Chemistry. 2019 ; Vol. 294, No. 47. pp. 17951-17961.
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