Abstract
Dominant-negative TGF-β receptor II (dnTGF-βRII) mice spontaneously develop an autoimmune cholangitis resembling human primary biliary cirrhosis (PBC). Interestingly, the dominant-negative TGF-β receptor is expressed by both CD4+ and CD8+ T cells and leads to greatly reduced (but not absent) TGF-β signaling resulting in T cell intrinsic cell mediated autoimmunity. However, the mechanisms of the T cell dysregulation remain unclear. Recently it has been shown that TGF-β signaling is intimately involved with miRNA biogenesis and control. Herein we show that lack of T cell TGF-β signaling leads to down regulation of T cell miRNAs but up-regulation of the key inflammatory miRNA 21. Furthermore, the expression of miR-21 from hepatic effector CD8+ T cells is significantly higher than in the same subsets isolated from spleen and mesenteric lymph nodes of the dnTGF-βRII mice. Previous studies indicate that miR-21 increases the synthesis of IFN-γ and IL-17A by T cells and suppresses apoptosis via programmed cell death protein 4 (PDCD4). Data presented herein demonstrate that transfecting w.t. B6 T cell subsets with miR-21 resulted in up-regulation of the inflammatory cytokines TNF-α and IFN-γ, thus partly replicating the dnTGF-βRII T cell phenotype. In conclusion, these data suggest miR-21 plays a critical role in the production of pro-inflammatory cytokines in dnTGF-βRII mice, which could be a contributing factor for the development of the organ-specific autoimmune cholangitis and colitis in this murine model of human PBC.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 111-119 |
| Number of pages | 9 |
| Journal | Journal of Autoimmunity |
| Volume | 41 |
| DOIs | |
| State | Published - Mar 2013 |
Fingerprint
Keywords
- Autoimmunity
- Cholangitis
- Colitis
- Inflammatory bowel disease
- MicroRNA
- MiR-21
- Primary biliary cirrhosis
ASJC Scopus subject areas
- Immunology
- Immunology and Allergy
Cite this
Overexpression of microRNA-21 is associated with elevated pro-inflammatory cytokines in dominant-negative TGF-β receptor type II mouse. / Ando, Yugo; Yang, Guo Xiang; Kenny, Thomas P.; Kawata, Kazuhito; Zhang, Weici; Huang, Wenting; Leung, Patrick S; Lian, Zhe Xiong; Okazaki, Kazuichi; Ansari, Aftab A.; He, Xiaosong; Invernizzi, Pietro; Ridgway, William M.; Lu, Qianjin; Gershwin, M. Eric.
In: Journal of Autoimmunity, Vol. 41, 03.2013, p. 111-119.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Overexpression of microRNA-21 is associated with elevated pro-inflammatory cytokines in dominant-negative TGF-β receptor type II mouse
AU - Ando, Yugo
AU - Yang, Guo Xiang
AU - Kenny, Thomas P.
AU - Kawata, Kazuhito
AU - Zhang, Weici
AU - Huang, Wenting
AU - Leung, Patrick S
AU - Lian, Zhe Xiong
AU - Okazaki, Kazuichi
AU - Ansari, Aftab A.
AU - He, Xiaosong
AU - Invernizzi, Pietro
AU - Ridgway, William M.
AU - Lu, Qianjin
AU - Gershwin, M. Eric
PY - 2013/3
Y1 - 2013/3
N2 - Dominant-negative TGF-β receptor II (dnTGF-βRII) mice spontaneously develop an autoimmune cholangitis resembling human primary biliary cirrhosis (PBC). Interestingly, the dominant-negative TGF-β receptor is expressed by both CD4+ and CD8+ T cells and leads to greatly reduced (but not absent) TGF-β signaling resulting in T cell intrinsic cell mediated autoimmunity. However, the mechanisms of the T cell dysregulation remain unclear. Recently it has been shown that TGF-β signaling is intimately involved with miRNA biogenesis and control. Herein we show that lack of T cell TGF-β signaling leads to down regulation of T cell miRNAs but up-regulation of the key inflammatory miRNA 21. Furthermore, the expression of miR-21 from hepatic effector CD8+ T cells is significantly higher than in the same subsets isolated from spleen and mesenteric lymph nodes of the dnTGF-βRII mice. Previous studies indicate that miR-21 increases the synthesis of IFN-γ and IL-17A by T cells and suppresses apoptosis via programmed cell death protein 4 (PDCD4). Data presented herein demonstrate that transfecting w.t. B6 T cell subsets with miR-21 resulted in up-regulation of the inflammatory cytokines TNF-α and IFN-γ, thus partly replicating the dnTGF-βRII T cell phenotype. In conclusion, these data suggest miR-21 plays a critical role in the production of pro-inflammatory cytokines in dnTGF-βRII mice, which could be a contributing factor for the development of the organ-specific autoimmune cholangitis and colitis in this murine model of human PBC.
AB - Dominant-negative TGF-β receptor II (dnTGF-βRII) mice spontaneously develop an autoimmune cholangitis resembling human primary biliary cirrhosis (PBC). Interestingly, the dominant-negative TGF-β receptor is expressed by both CD4+ and CD8+ T cells and leads to greatly reduced (but not absent) TGF-β signaling resulting in T cell intrinsic cell mediated autoimmunity. However, the mechanisms of the T cell dysregulation remain unclear. Recently it has been shown that TGF-β signaling is intimately involved with miRNA biogenesis and control. Herein we show that lack of T cell TGF-β signaling leads to down regulation of T cell miRNAs but up-regulation of the key inflammatory miRNA 21. Furthermore, the expression of miR-21 from hepatic effector CD8+ T cells is significantly higher than in the same subsets isolated from spleen and mesenteric lymph nodes of the dnTGF-βRII mice. Previous studies indicate that miR-21 increases the synthesis of IFN-γ and IL-17A by T cells and suppresses apoptosis via programmed cell death protein 4 (PDCD4). Data presented herein demonstrate that transfecting w.t. B6 T cell subsets with miR-21 resulted in up-regulation of the inflammatory cytokines TNF-α and IFN-γ, thus partly replicating the dnTGF-βRII T cell phenotype. In conclusion, these data suggest miR-21 plays a critical role in the production of pro-inflammatory cytokines in dnTGF-βRII mice, which could be a contributing factor for the development of the organ-specific autoimmune cholangitis and colitis in this murine model of human PBC.
KW - Autoimmunity
KW - Cholangitis
KW - Colitis
KW - Inflammatory bowel disease
KW - MicroRNA
KW - MiR-21
KW - Primary biliary cirrhosis
UR - http://www.scopus.com/inward/record.url?scp=84875917033&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84875917033&partnerID=8YFLogxK
U2 - 10.1016/j.jaut.2012.12.013
DO - 10.1016/j.jaut.2012.12.013
M3 - Article
C2 - 23395552
AN - SCOPUS:84875917033
VL - 41
SP - 111
EP - 119
JO - Journal of Autoimmunity
JF - Journal of Autoimmunity
SN - 0896-8411
ER -