UBASH3A Interacts with PTPN22 to Regulate <i>IL2</i> Expression and Risk for Type 1 Diabetes
UBASH3A is a negative regulator of T cell activation and IL-2 production and plays key roles in autoimmunity. Although previous studies revealed the individual effects of UBASH3A on risk for type 1 diabetes (T1D; a common autoimmune disease), the relationship of UBASH3A with other T1D risk factors r...
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| Format: | Article |
| Language: | English |
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MDPI AG
2023-05-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/24/10/8671 |
| _version_ | 1797599815358480384 |
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| author | Jeremy R. B. Newman Patrick Concannon Yan Ge |
| author_facet | Jeremy R. B. Newman Patrick Concannon Yan Ge |
| author_sort | Jeremy R. B. Newman |
| collection | DOAJ |
| description | UBASH3A is a negative regulator of T cell activation and IL-2 production and plays key roles in autoimmunity. Although previous studies revealed the individual effects of UBASH3A on risk for type 1 diabetes (T1D; a common autoimmune disease), the relationship of UBASH3A with other T1D risk factors remains largely unknown. Given that another well-known T1D risk factor, PTPN22, also inhibits T cell activation and IL-2 production, we investigated the relationship between UBASH3A and PTPN22. We found that UBASH3A, via its Src homology 3 (SH3) domain, physically interacts with PTPN22 in T cells, and that this interaction is not altered by the T1D risk coding variant rs2476601 in <i>PTPN22</i>. Furthermore, our analysis of RNA-seq data from T1D cases showed that the amounts of <i>UBASH3A</i> and <i>PTPN22</i> transcripts exert a cooperative effect on <i>IL2</i> expression in human primary CD8<sup>+</sup> T cells. Finally, our genetic association analyses revealed that two independent T1D risk variants, rs11203203 in <i>UBASH3A</i> and rs2476601 in <i>PTPN22</i>, interact statistically, jointly affecting risk for T1D. In summary, our study reveals novel interactions, both biochemical and statistical, between two independent T1D risk loci, and suggests how these interactions may affect T cell function and increase risk for T1D. |
| first_indexed | 2024-03-11T03:40:37Z |
| format | Article |
| id | doaj.art-7bfdea4e54db416b9b09e114bf8eb162 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-11T03:40:37Z |
| publishDate | 2023-05-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-7bfdea4e54db416b9b09e114bf8eb1622023-11-18T01:39:46ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672023-05-012410867110.3390/ijms24108671UBASH3A Interacts with PTPN22 to Regulate <i>IL2</i> Expression and Risk for Type 1 DiabetesJeremy R. B. Newman0Patrick Concannon1Yan Ge2Department of Molecular Genetics & Microbiology, University of Florida, Gainesville, FL 32610, USAGenetics Institute, University of Florida, Gainesville, FL 32610, USAGenetics Institute, University of Florida, Gainesville, FL 32610, USAUBASH3A is a negative regulator of T cell activation and IL-2 production and plays key roles in autoimmunity. Although previous studies revealed the individual effects of UBASH3A on risk for type 1 diabetes (T1D; a common autoimmune disease), the relationship of UBASH3A with other T1D risk factors remains largely unknown. Given that another well-known T1D risk factor, PTPN22, also inhibits T cell activation and IL-2 production, we investigated the relationship between UBASH3A and PTPN22. We found that UBASH3A, via its Src homology 3 (SH3) domain, physically interacts with PTPN22 in T cells, and that this interaction is not altered by the T1D risk coding variant rs2476601 in <i>PTPN22</i>. Furthermore, our analysis of RNA-seq data from T1D cases showed that the amounts of <i>UBASH3A</i> and <i>PTPN22</i> transcripts exert a cooperative effect on <i>IL2</i> expression in human primary CD8<sup>+</sup> T cells. Finally, our genetic association analyses revealed that two independent T1D risk variants, rs11203203 in <i>UBASH3A</i> and rs2476601 in <i>PTPN22</i>, interact statistically, jointly affecting risk for T1D. In summary, our study reveals novel interactions, both biochemical and statistical, between two independent T1D risk loci, and suggests how these interactions may affect T cell function and increase risk for T1D.https://www.mdpi.com/1422-0067/24/10/8671UBASH3APTPN22IL-2type 1 diabetesautoimmunityrs11203203 |
| spellingShingle | Jeremy R. B. Newman Patrick Concannon Yan Ge UBASH3A Interacts with PTPN22 to Regulate <i>IL2</i> Expression and Risk for Type 1 Diabetes International Journal of Molecular Sciences UBASH3A PTPN22 IL-2 type 1 diabetes autoimmunity rs11203203 |
| title | UBASH3A Interacts with PTPN22 to Regulate <i>IL2</i> Expression and Risk for Type 1 Diabetes |
| title_full | UBASH3A Interacts with PTPN22 to Regulate <i>IL2</i> Expression and Risk for Type 1 Diabetes |
| title_fullStr | UBASH3A Interacts with PTPN22 to Regulate <i>IL2</i> Expression and Risk for Type 1 Diabetes |
| title_full_unstemmed | UBASH3A Interacts with PTPN22 to Regulate <i>IL2</i> Expression and Risk for Type 1 Diabetes |
| title_short | UBASH3A Interacts with PTPN22 to Regulate <i>IL2</i> Expression and Risk for Type 1 Diabetes |
| title_sort | ubash3a interacts with ptpn22 to regulate i il2 i expression and risk for type 1 diabetes |
| topic | UBASH3A PTPN22 IL-2 type 1 diabetes autoimmunity rs11203203 |
| url | https://www.mdpi.com/1422-0067/24/10/8671 |
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