Abstract
Understanding the mechanisms that lead to autoimmunity is critical for defining potential therapeutic pathways. In this regard there have been considerable efforts in investigating the interacting roles of TGF-β and IL-2 on the function regulatory T cells. We have taken advantage of dnTGF-βRII Il2ra-/- (abbreviated as Il2ra-/-Tg) mouse model, which allows a direct mechanistic approach to define the relative roles of TGF-β and IL-2 on Treg development. Il2ra-/-Tg mice spontaneously developed multi-organ autoimmune diseases with expansion of pathogenic T cells and enhanced germinal center response at 3-4 weeks of age. Importantly, peripheral Treg cells from Il2ra-/-Tg mice demonstrated an activated Th1-like stable phenotype and normal in vitro suppressive function, while thymus Treg increased but manifested decreased suppressive function. Interestingly, neither thymus nor peripheral Treg cells of Il2ra-/-Tg mice contained Neuropilin-1+ or PD-1hi phenotype, resulting in defective follicular regulatory T (Tfr) cell development. Such defective Tfr development led to elevated follicular T helper cells, enhanced germinal center responses and increased plasma cell infiltration. These data demonstrate an important synergetic role of TGF-β and IL-2 in the generation, activation and stability of Treg cells, as well as their subsequent development into Tfr cells.
| Original language | English (US) |
|---|---|
| Pages (from-to) | e2439 |
| Journal | Cell death & disease |
| Volume | 7 |
| Issue number | 10 |
| DOIs | |
| State | Published - Oct 27 2016 |
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ASJC Scopus subject areas
- Immunology
- Cellular and Molecular Neuroscience
- Cell Biology
- Cancer Research
Cite this
Block of both TGF-β and IL-2 signaling impedes Neurophilin-1+ regulatory T cell and follicular regulatory T cell development. / Li, Liang; Yang, Shu Han; Yao, Yuan; Xie, Yu Qing; Yang, Yan Qing; Wang, Yin Hu; Yin, Xue Ying; Ma, Hong Di; Gershwin, M. Eric; Lian, Zhe Xiong.
In: Cell death & disease, Vol. 7, No. 10, 27.10.2016, p. e2439.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Block of both TGF-β and IL-2 signaling impedes Neurophilin-1+ regulatory T cell and follicular regulatory T cell development
AU - Li, Liang
AU - Yang, Shu Han
AU - Yao, Yuan
AU - Xie, Yu Qing
AU - Yang, Yan Qing
AU - Wang, Yin Hu
AU - Yin, Xue Ying
AU - Ma, Hong Di
AU - Gershwin, M. Eric
AU - Lian, Zhe Xiong
PY - 2016/10/27
Y1 - 2016/10/27
N2 - Understanding the mechanisms that lead to autoimmunity is critical for defining potential therapeutic pathways. In this regard there have been considerable efforts in investigating the interacting roles of TGF-β and IL-2 on the function regulatory T cells. We have taken advantage of dnTGF-βRII Il2ra-/- (abbreviated as Il2ra-/-Tg) mouse model, which allows a direct mechanistic approach to define the relative roles of TGF-β and IL-2 on Treg development. Il2ra-/-Tg mice spontaneously developed multi-organ autoimmune diseases with expansion of pathogenic T cells and enhanced germinal center response at 3-4 weeks of age. Importantly, peripheral Treg cells from Il2ra-/-Tg mice demonstrated an activated Th1-like stable phenotype and normal in vitro suppressive function, while thymus Treg increased but manifested decreased suppressive function. Interestingly, neither thymus nor peripheral Treg cells of Il2ra-/-Tg mice contained Neuropilin-1+ or PD-1hi phenotype, resulting in defective follicular regulatory T (Tfr) cell development. Such defective Tfr development led to elevated follicular T helper cells, enhanced germinal center responses and increased plasma cell infiltration. These data demonstrate an important synergetic role of TGF-β and IL-2 in the generation, activation and stability of Treg cells, as well as their subsequent development into Tfr cells.
AB - Understanding the mechanisms that lead to autoimmunity is critical for defining potential therapeutic pathways. In this regard there have been considerable efforts in investigating the interacting roles of TGF-β and IL-2 on the function regulatory T cells. We have taken advantage of dnTGF-βRII Il2ra-/- (abbreviated as Il2ra-/-Tg) mouse model, which allows a direct mechanistic approach to define the relative roles of TGF-β and IL-2 on Treg development. Il2ra-/-Tg mice spontaneously developed multi-organ autoimmune diseases with expansion of pathogenic T cells and enhanced germinal center response at 3-4 weeks of age. Importantly, peripheral Treg cells from Il2ra-/-Tg mice demonstrated an activated Th1-like stable phenotype and normal in vitro suppressive function, while thymus Treg increased but manifested decreased suppressive function. Interestingly, neither thymus nor peripheral Treg cells of Il2ra-/-Tg mice contained Neuropilin-1+ or PD-1hi phenotype, resulting in defective follicular regulatory T (Tfr) cell development. Such defective Tfr development led to elevated follicular T helper cells, enhanced germinal center responses and increased plasma cell infiltration. These data demonstrate an important synergetic role of TGF-β and IL-2 in the generation, activation and stability of Treg cells, as well as their subsequent development into Tfr cells.
UR - http://www.scopus.com/inward/record.url?scp=85028632433&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85028632433&partnerID=8YFLogxK
U2 - 10.1038/cddis.2016.348
DO - 10.1038/cddis.2016.348
M3 - Article
C2 - 27787514
AN - SCOPUS:85028632433
VL - 7
SP - e2439
JO - Cell Death and Disease
JF - Cell Death and Disease
SN - 2041-4889
IS - 10
ER -