Mesenchymal stem cells prevent overwhelming inflammation and reduce infection severity via recruiting CXCR3+ regulatory T cells
Abstract Objectives Mesenchymal stem cells (MSCs) have shown great potential in treating autoimmune diseases (ADs). Unlike the traditional immunosuppressants, which inadvertently impair patients' antimicrobial immunity, MSCs reduce the incidence and duration of respiratory infection. However, t...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2020-01-01
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| Series: | Clinical & Translational Immunology |
| Subjects: | |
| Online Access: | https://doi.org/10.1002/cti2.1181 |
| _version_ | 1811324738079817728 |
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| author | Wenchao Li Weiwei Chen Saisai Huang Genhong Yao Xiaojun Tang Lingyun Sun |
| author_facet | Wenchao Li Weiwei Chen Saisai Huang Genhong Yao Xiaojun Tang Lingyun Sun |
| author_sort | Wenchao Li |
| collection | DOAJ |
| description | Abstract Objectives Mesenchymal stem cells (MSCs) have shown great potential in treating autoimmune diseases (ADs). Unlike the traditional immunosuppressants, which inadvertently impair patients' antimicrobial immunity, MSCs reduce the incidence and duration of respiratory infection. However, the underlying mechanisms are unknown. Methods To investigate how MSCs regulate the lung immunity and improve the defence against respiratory infection, we infected MSC‐treated wild‐type and lupus‐prone mice with Haemophilus influenzae intranasally and determined the clearance of bacteria. Tissue damage and inflammatory cytokines were measured by H&E staining and ELISA separately. Immune cell subsets in the tissues were analysed by flow cytometry. Results MSC pretreatment prevented overwhelming inflammation and accelerated bacterial clearance in both wild‐type and lupus‐prone mice. Tregs increased dramatically in the lung after MSC treatment. Adoptive transfer of Tregs isolated from MSC‐treated mice offered similar protection, while deletion of Tregs abrogated the protective effects of MSCs. The majority of the intravenously injected MSCs were engulfed by lung phagocytes, which in turn produced CXCL9 and CXCL10 and recruited tremendous CXCR3+ Tregs into the lung. Compared with their CXCR3− counterparts, CXCR3+ Tregs displayed enhanced proliferation and stronger inhibitory functions. Neutralisation of CXCL9 and CXCL10 significantly downregulated the migration of CXCR3+ Tregs and eliminated the benefits of MSC pretreatment. Conclusion Here, we showed that by recruiting CXCR3+ Tregs, MSC treatment restricted the overactivation of inflammatory responses and prevented severe symptoms caused by infection. By discovering this novel property of MSCs, our study sheds light on optimising long‐term immunosuppressive regimen for autoimmune diseases and other immune disorders. |
| first_indexed | 2024-04-13T14:19:42Z |
| format | Article |
| id | doaj.art-5ffbdaffeb6f4aab95093e63b182f74e |
| institution | Directory Open Access Journal |
| issn | 2050-0068 |
| language | English |
| last_indexed | 2024-04-13T14:19:42Z |
| publishDate | 2020-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Clinical & Translational Immunology |
| spelling | doaj.art-5ffbdaffeb6f4aab95093e63b182f74e2022-12-22T02:43:30ZengWileyClinical & Translational Immunology2050-00682020-01-01910n/an/a10.1002/cti2.1181Mesenchymal stem cells prevent overwhelming inflammation and reduce infection severity via recruiting CXCR3+ regulatory T cellsWenchao Li0Weiwei Chen1Saisai Huang2Genhong Yao3Xiaojun Tang4Lingyun Sun5Department of Rheumatology and Immunology The Affiliated Drum Tower Hospital of Nanjing University Medical School Nanjing ChinaDepartment of Rheumatology and Immunology The Affiliated Drum Tower Hospital of Nanjing University Medical School Nanjing ChinaDepartment of Rheumatology and Immunology The Affiliated Drum Tower Hospital of Nanjing University Medical School Nanjing ChinaDepartment of Rheumatology and Immunology The Affiliated Drum Tower Hospital of Nanjing University Medical School Nanjing ChinaDepartment of Rheumatology and Immunology The Affiliated Drum Tower Hospital of Nanjing University Medical School Nanjing ChinaDepartment of Rheumatology and Immunology The Affiliated Drum Tower Hospital of Nanjing University Medical School Nanjing ChinaAbstract Objectives Mesenchymal stem cells (MSCs) have shown great potential in treating autoimmune diseases (ADs). Unlike the traditional immunosuppressants, which inadvertently impair patients' antimicrobial immunity, MSCs reduce the incidence and duration of respiratory infection. However, the underlying mechanisms are unknown. Methods To investigate how MSCs regulate the lung immunity and improve the defence against respiratory infection, we infected MSC‐treated wild‐type and lupus‐prone mice with Haemophilus influenzae intranasally and determined the clearance of bacteria. Tissue damage and inflammatory cytokines were measured by H&E staining and ELISA separately. Immune cell subsets in the tissues were analysed by flow cytometry. Results MSC pretreatment prevented overwhelming inflammation and accelerated bacterial clearance in both wild‐type and lupus‐prone mice. Tregs increased dramatically in the lung after MSC treatment. Adoptive transfer of Tregs isolated from MSC‐treated mice offered similar protection, while deletion of Tregs abrogated the protective effects of MSCs. The majority of the intravenously injected MSCs were engulfed by lung phagocytes, which in turn produced CXCL9 and CXCL10 and recruited tremendous CXCR3+ Tregs into the lung. Compared with their CXCR3− counterparts, CXCR3+ Tregs displayed enhanced proliferation and stronger inhibitory functions. Neutralisation of CXCL9 and CXCL10 significantly downregulated the migration of CXCR3+ Tregs and eliminated the benefits of MSC pretreatment. Conclusion Here, we showed that by recruiting CXCR3+ Tregs, MSC treatment restricted the overactivation of inflammatory responses and prevented severe symptoms caused by infection. By discovering this novel property of MSCs, our study sheds light on optimising long‐term immunosuppressive regimen for autoimmune diseases and other immune disorders.https://doi.org/10.1002/cti2.1181autoimmune diseaseCXCR3mesenchymal stem cellsrespiratory infectionTreg cells |
| spellingShingle | Wenchao Li Weiwei Chen Saisai Huang Genhong Yao Xiaojun Tang Lingyun Sun Mesenchymal stem cells prevent overwhelming inflammation and reduce infection severity via recruiting CXCR3+ regulatory T cells Clinical & Translational Immunology autoimmune disease CXCR3 mesenchymal stem cells respiratory infection Treg cells |
| title | Mesenchymal stem cells prevent overwhelming inflammation and reduce infection severity via recruiting CXCR3+ regulatory T cells |
| title_full | Mesenchymal stem cells prevent overwhelming inflammation and reduce infection severity via recruiting CXCR3+ regulatory T cells |
| title_fullStr | Mesenchymal stem cells prevent overwhelming inflammation and reduce infection severity via recruiting CXCR3+ regulatory T cells |
| title_full_unstemmed | Mesenchymal stem cells prevent overwhelming inflammation and reduce infection severity via recruiting CXCR3+ regulatory T cells |
| title_short | Mesenchymal stem cells prevent overwhelming inflammation and reduce infection severity via recruiting CXCR3+ regulatory T cells |
| title_sort | mesenchymal stem cells prevent overwhelming inflammation and reduce infection severity via recruiting cxcr3 regulatory t cells |
| topic | autoimmune disease CXCR3 mesenchymal stem cells respiratory infection Treg cells |
| url | https://doi.org/10.1002/cti2.1181 |
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