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| Status |
Public on Mar 15, 2017 |
| Title |
Lymphocyte Activation Gene-3 limits regulatory T cell proliferation and function in autoimmune diabetes |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Inhibitory receptors (Irs) are pivotal in controlling T cell homeostasis because of their intrinsic regulation of conventional T (Tconv) cell proliferation, viability and function. However, the role of Irs on regulatory T (Treg) cells remains obscure, as they could be required for suppressive activity and/or limit Treg cell function. We evaluated the role of Lymphocyte Activation Gene-3 (LAG3, CD223) on Treg cells by generating mice in which LAG3 is absent on the cell surface of Treg cells in a murine model of Type 1 Diabetes. Surprisingly, mice that lacked LAG3 expression on Treg cells exhibited reduced autoimmune diabetes, consistent with enhanced Treg cell proliferation and function. Whereas the transcriptional landscape of peripheral wild-type (WT) and Lag3-deficient Treg cells was largely comparable, substantial differences between intra-islet Treg cells were evident and involved a subset of genes and pathways that promote Treg cell maintenance and function. Consistent with these observations, Lag3-deficient Treg cells out-competed WT Treg cells in the islets but not in the periphery in co-transfer experiments due to enhanced IL2-Stat5 signaling and Eos expression. Our study suggests that LAG3 intrinsically limits Treg cell proliferation and function at inflamed pancreas, promotes autoimmunity in a chronic autoimmune-prone environment and may contribute to Treg cell insufficiency in autoimmune disease
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| Overall design |
Wt and Lag3 deficient Tregs from islets and non-draining lymph nodes NDLN in an autoimmune diabetes model.
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| Contributor(s) |
Chikina M |
| Citation missing |
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| |
| Submission date |
Feb 06, 2017 |
| Last update date |
May 15, 2019 |
| Contact name |
Maria Chikina |
| E-mail(s) |
mchikina@gmail.com
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| Organization name |
University of Pittsburgh
|
| Street address |
3501 5th ave
|
| City |
Pittsburgh |
| State/province |
PA |
| ZIP/Postal code |
15260 |
| Country |
USA |
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| Platforms (1) |
| GPL19057 |
Illumina NextSeq 500 (Mus musculus) |
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| Samples (12)
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| Relations |
| BioProject |
PRJNA371501 |
| SRA |
SRP098941 |
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