Interleukin-30 Suppresses Not Only CD4<sup>+</sup> T Cells but Also Regulatory T Cells in Murine Primary Biliary Cholangitis
Primary biliary cholangitis (PBC) is a chronic liver autoimmune disease with augmented T helper (Th) 1 and corresponding cytokine IFN-γ immune responses. Using 2-octynoic acid (2-OA) coupled to OVA (2-OA-OVA)-induced mouse models of autoimmune cholangitis (inducible chemical xenobiotic models of PBC...
| Main Authors: | , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2021-08-01
|
| Series: | Biomedicines |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2227-9059/9/8/1031 |
| _version_ | 1797524574646042624 |
|---|---|
| author | Hung-Wen Chen Chia-I. Lin Ya-Hui Chuang |
| author_facet | Hung-Wen Chen Chia-I. Lin Ya-Hui Chuang |
| author_sort | Hung-Wen Chen |
| collection | DOAJ |
| description | Primary biliary cholangitis (PBC) is a chronic liver autoimmune disease with augmented T helper (Th) 1 and corresponding cytokine IFN-γ immune responses. Using 2-octynoic acid (2-OA) coupled to OVA (2-OA-OVA)-induced mouse models of autoimmune cholangitis (inducible chemical xenobiotic models of PBC), our previous study demonstrated that overexpression of IFN-γ in the model mice enhanced liver inflammation upon disease initiation, but subsequently led to the suppression of chronic inflammation with an increase in interleukin-30 (IL-30) levels. In this study, we investigated whether IL-30 had an immunosuppressive function and whether it could be part of an immune therapeutic regimen for PBC, by treating model mice with murine IL-30-expressing recombinant adeno-associated virus (AAV-mIL-30). We first defined the effects of AAV-mIL-30 in vivo by administering it to a well-known concanavalin A (ConA)-induced hepatitis model of mice and found that AAV-mIL-30 reduced the numbers of activated CD25<sup>+</sup>CD4<sup>+</sup> T cells and the levels of serum IFN-γ and IL-12. In autoimmune cholangitis, decreased numbers of activated CD4<sup>+</sup> T cells and Foxp3<sup>+</sup> regulatory T cells were noted in the mice treated with AAV-mIL-30 at 3 weeks after the 2-OA-OVA immunization. Treatment with IL-30 did not change the features of autoimmune cholangitis including autoantibodies, cell infiltration, and collagen deposition in the liver at 11 weeks of examination. However, increased levels of cytokines and chemokines were observed. These results suggest that IL-30 suppresses not only CD4<sup>+</sup> T cells but also regulatory T cells. Additionally, the administration of IL-30 did not suppress liver inflammation in the murine model of PBC. |
| first_indexed | 2024-03-10T08:59:22Z |
| format | Article |
| id | doaj.art-5657eb9edc8c4142ab183c51ff8805d8 |
| institution | Directory Open Access Journal |
| issn | 2227-9059 |
| language | English |
| last_indexed | 2024-03-10T08:59:22Z |
| publishDate | 2021-08-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Biomedicines |
| spelling | doaj.art-5657eb9edc8c4142ab183c51ff8805d82023-11-22T06:53:36ZengMDPI AGBiomedicines2227-90592021-08-0198103110.3390/biomedicines9081031Interleukin-30 Suppresses Not Only CD4<sup>+</sup> T Cells but Also Regulatory T Cells in Murine Primary Biliary CholangitisHung-Wen Chen0Chia-I. Lin1Ya-Hui Chuang2Department of Clinical Laboratory Sciences and Medical Biotechnology, College of Medicine, National Taiwan University, Taipei 10617, TaiwanDepartment of Clinical Laboratory Sciences and Medical Biotechnology, College of Medicine, National Taiwan University, Taipei 10617, TaiwanDepartment of Clinical Laboratory Sciences and Medical Biotechnology, College of Medicine, National Taiwan University, Taipei 10617, TaiwanPrimary biliary cholangitis (PBC) is a chronic liver autoimmune disease with augmented T helper (Th) 1 and corresponding cytokine IFN-γ immune responses. Using 2-octynoic acid (2-OA) coupled to OVA (2-OA-OVA)-induced mouse models of autoimmune cholangitis (inducible chemical xenobiotic models of PBC), our previous study demonstrated that overexpression of IFN-γ in the model mice enhanced liver inflammation upon disease initiation, but subsequently led to the suppression of chronic inflammation with an increase in interleukin-30 (IL-30) levels. In this study, we investigated whether IL-30 had an immunosuppressive function and whether it could be part of an immune therapeutic regimen for PBC, by treating model mice with murine IL-30-expressing recombinant adeno-associated virus (AAV-mIL-30). We first defined the effects of AAV-mIL-30 in vivo by administering it to a well-known concanavalin A (ConA)-induced hepatitis model of mice and found that AAV-mIL-30 reduced the numbers of activated CD25<sup>+</sup>CD4<sup>+</sup> T cells and the levels of serum IFN-γ and IL-12. In autoimmune cholangitis, decreased numbers of activated CD4<sup>+</sup> T cells and Foxp3<sup>+</sup> regulatory T cells were noted in the mice treated with AAV-mIL-30 at 3 weeks after the 2-OA-OVA immunization. Treatment with IL-30 did not change the features of autoimmune cholangitis including autoantibodies, cell infiltration, and collagen deposition in the liver at 11 weeks of examination. However, increased levels of cytokines and chemokines were observed. These results suggest that IL-30 suppresses not only CD4<sup>+</sup> T cells but also regulatory T cells. Additionally, the administration of IL-30 did not suppress liver inflammation in the murine model of PBC.https://www.mdpi.com/2227-9059/9/8/1031primary biliary cholangitisautoimmune diseaseinterleukin-30immune therapyCD4<sup>+</sup> T cells |
| spellingShingle | Hung-Wen Chen Chia-I. Lin Ya-Hui Chuang Interleukin-30 Suppresses Not Only CD4<sup>+</sup> T Cells but Also Regulatory T Cells in Murine Primary Biliary Cholangitis Biomedicines primary biliary cholangitis autoimmune disease interleukin-30 immune therapy CD4<sup>+</sup> T cells |
| title | Interleukin-30 Suppresses Not Only CD4<sup>+</sup> T Cells but Also Regulatory T Cells in Murine Primary Biliary Cholangitis |
| title_full | Interleukin-30 Suppresses Not Only CD4<sup>+</sup> T Cells but Also Regulatory T Cells in Murine Primary Biliary Cholangitis |
| title_fullStr | Interleukin-30 Suppresses Not Only CD4<sup>+</sup> T Cells but Also Regulatory T Cells in Murine Primary Biliary Cholangitis |
| title_full_unstemmed | Interleukin-30 Suppresses Not Only CD4<sup>+</sup> T Cells but Also Regulatory T Cells in Murine Primary Biliary Cholangitis |
| title_short | Interleukin-30 Suppresses Not Only CD4<sup>+</sup> T Cells but Also Regulatory T Cells in Murine Primary Biliary Cholangitis |
| title_sort | interleukin 30 suppresses not only cd4 sup sup t cells but also regulatory t cells in murine primary biliary cholangitis |
| topic | primary biliary cholangitis autoimmune disease interleukin-30 immune therapy CD4<sup>+</sup> T cells |
| url | https://www.mdpi.com/2227-9059/9/8/1031 |
| work_keys_str_mv | AT hungwenchen interleukin30suppressesnotonlycd4supsuptcellsbutalsoregulatorytcellsinmurineprimarybiliarycholangitis AT chiailin interleukin30suppressesnotonlycd4supsuptcellsbutalsoregulatorytcellsinmurineprimarybiliarycholangitis AT yahuichuang interleukin30suppressesnotonlycd4supsuptcellsbutalsoregulatorytcellsinmurineprimarybiliarycholangitis |