Abstract
IL-17 is known to be a cytokine mainly secreted from Th17 cells, which well associate with autoimmune inflammatory responses. In the generation of Th17 cells, RORc and RORa have pivotal roles in controlling the transcription of Il17. We speculated additional regulation in Il17a transcription and randomly screened a 6344 clone cDNA library to identify specific modulators for Il17a promoter activity. After the screen, the E3 ubiquitin ligases SIAH1 and SIAH2 were investigated further and confirmed to increase Il17a promoter activity in a T-cell line and to promote Th17 development ex vivo. This enhancement was a consequence of enhanced expression of hypoxia-inducible factor- 1a (HIF-1a) protein, which is reported to directly regulate expression of Il17a and Rorgt at the transcriptional level. In the absence of HIF-1a, both ubiquitin ligases had little effect on Th17 cell differentiation. These results suggest that the SIAH1 and SIAH2 play a pivotal role to promote Th17 cell differentiation through maintaining the stability of HIF-1a protein.
| Original language | English |
|---|---|
| Article number | dxx014 |
| Pages (from-to) | 133-143 |
| Number of pages | 11 |
| Journal | International Immunology |
| Volume | 29 |
| Issue number | 3 |
| DOIs | |
| Publication status | Published - 2017 Mar 1 |
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Keywords
- Autoimmune
- HIF-1
- Signaling
- T17
ASJC Scopus subject areas
- Immunology
Cite this
E3 ubiquitin ligases SIAH1/2 regulate hypoxiainducible factor-1 (HIF-1)-mediated Th17 cell differentiation. / Matsui-Hasumi, Akiko; Sato, Yayoi; Uto-Konomi, Ayako; Yamashita, Satoshi; Uehori, Junji; Yoshimura, Akihiko; Yamashita, Masakatsu; Asahara, Hiroshi; Suzuki, Shinobu; Kubo, Masato.
In: International Immunology, Vol. 29, No. 3, dxx014, 01.03.2017, p. 133-143.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - E3 ubiquitin ligases SIAH1/2 regulate hypoxiainducible factor-1 (HIF-1)-mediated Th17 cell differentiation
AU - Matsui-Hasumi, Akiko
AU - Sato, Yayoi
AU - Uto-Konomi, Ayako
AU - Yamashita, Satoshi
AU - Uehori, Junji
AU - Yoshimura, Akihiko
AU - Yamashita, Masakatsu
AU - Asahara, Hiroshi
AU - Suzuki, Shinobu
AU - Kubo, Masato
PY - 2017/3/1
Y1 - 2017/3/1
N2 - IL-17 is known to be a cytokine mainly secreted from Th17 cells, which well associate with autoimmune inflammatory responses. In the generation of Th17 cells, RORc and RORa have pivotal roles in controlling the transcription of Il17. We speculated additional regulation in Il17a transcription and randomly screened a 6344 clone cDNA library to identify specific modulators for Il17a promoter activity. After the screen, the E3 ubiquitin ligases SIAH1 and SIAH2 were investigated further and confirmed to increase Il17a promoter activity in a T-cell line and to promote Th17 development ex vivo. This enhancement was a consequence of enhanced expression of hypoxia-inducible factor- 1a (HIF-1a) protein, which is reported to directly regulate expression of Il17a and Rorgt at the transcriptional level. In the absence of HIF-1a, both ubiquitin ligases had little effect on Th17 cell differentiation. These results suggest that the SIAH1 and SIAH2 play a pivotal role to promote Th17 cell differentiation through maintaining the stability of HIF-1a protein.
AB - IL-17 is known to be a cytokine mainly secreted from Th17 cells, which well associate with autoimmune inflammatory responses. In the generation of Th17 cells, RORc and RORa have pivotal roles in controlling the transcription of Il17. We speculated additional regulation in Il17a transcription and randomly screened a 6344 clone cDNA library to identify specific modulators for Il17a promoter activity. After the screen, the E3 ubiquitin ligases SIAH1 and SIAH2 were investigated further and confirmed to increase Il17a promoter activity in a T-cell line and to promote Th17 development ex vivo. This enhancement was a consequence of enhanced expression of hypoxia-inducible factor- 1a (HIF-1a) protein, which is reported to directly regulate expression of Il17a and Rorgt at the transcriptional level. In the absence of HIF-1a, both ubiquitin ligases had little effect on Th17 cell differentiation. These results suggest that the SIAH1 and SIAH2 play a pivotal role to promote Th17 cell differentiation through maintaining the stability of HIF-1a protein.
KW - Autoimmune
KW - HIF-1
KW - Signaling
KW - T17
UR - http://www.scopus.com/inward/record.url?scp=85019150567&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85019150567&partnerID=8YFLogxK
U2 - 10.1093/intimm/dxx014
DO - 10.1093/intimm/dxx014
M3 - Article
C2 - 28338984
AN - SCOPUS:85019150567
VL - 29
SP - 133
EP - 143
JO - International Immunology
JF - International Immunology
SN - 0953-8178
IS - 3
M1 - dxx014
ER -