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 language | English |
|---|---|
| Pages (from-to) | 17951-17961 |
| Number of pages | 11 |
| Journal | Journal of Biological Chemistry |
| Volume | 294 |
| Issue number | 47 |
| DOIs | |
| Publication status | Published - 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 journal › Article
}
TY - JOUR
T1 - NLRP3 negatively regulates Treg differentiation through Kpna2-mediated nuclear translocation
AU - Park, Su Ho
AU - Ham, Sunyoung
AU - Lee, Arim
AU - Möller, Andreas
AU - Kim, Tae Sung
PY - 2019/1/1
Y1 - 2019/1/1
N2 - 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.
AB - 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.
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U2 - 10.1074/jbc.RA119.010545
DO - 10.1074/jbc.RA119.010545
M3 - Article
C2 - 31597697
AN - SCOPUS:85075578495
VL - 294
SP - 17951
EP - 17961
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
SN - 0021-9258
IS - 47
ER -