IL-21 Rescues the Defect of IL-10-Producing Regulatory B Cells and Improves Allergic Asthma in DOCK8 Deficient Mice
Mutations in human DOCK8 cause a combined immunodeficiency syndrome characterized by allergic diseases such as asthma and food allergy. However, the underlying mechanism is unclear. Regulatory B (Breg) cells that produce IL-10 exert potent immunosuppressive functions in patients with allergic and au...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2021-11-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2021.695596/full |
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| author | Jinqiu Jiang Jinqiu Jiang Tao Qin Liang Zhang Qiao Liu Jiabin Wu Rongxin Dai Rongxin Dai Lina Zhou Qin Zhao Xiaoyan Luo Hua Wang Xiaodong Zhao Xiaodong Zhao |
| author_facet | Jinqiu Jiang Jinqiu Jiang Tao Qin Liang Zhang Qiao Liu Jiabin Wu Rongxin Dai Rongxin Dai Lina Zhou Qin Zhao Xiaoyan Luo Hua Wang Xiaodong Zhao Xiaodong Zhao |
| author_sort | Jinqiu Jiang |
| collection | DOAJ |
| description | Mutations in human DOCK8 cause a combined immunodeficiency syndrome characterized by allergic diseases such as asthma and food allergy. However, the underlying mechanism is unclear. Regulatory B (Breg) cells that produce IL-10 exert potent immunosuppressive functions in patients with allergic and autoimmune disorders. DOCK8-deficient B cells show diminished responses to TLR9 signaling, suggesting a possible defect in IL-10-producing Breg cells in those with DOCK8 deficiency, which may contribute to allergies. Here, we isolated peripheral blood mononuclear cells from DOCK8-deficient patients and generated a Dock8 KO mouse model to study the effect of DOCK8 deficiency on Breg cells. DOCK8-deficient patients and Dock8 KO mice harbored quantitative and qualitative defects in IL-10-producing Breg cells; these defects were caused by abnormal Dock8-/- CD4+ T cells. We found that recombinant murine (rm)IL-21 restored the function of Bregs both in vitro and in Dock8 KO mice, leading to reduced inflammatory cell infiltration of the lungs in a murine asthma model. Overall, the results provide new insight into the potential design of Breg-based or IL-21-based therapeutic strategies for allergic diseases, including asthma associated with DOCK8 deficiency. |
| first_indexed | 2024-12-20T05:24:47Z |
| format | Article |
| id | doaj.art-49b6f7f19bb44b6da39bf8023be1b23e |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-12-20T05:24:47Z |
| publishDate | 2021-11-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-49b6f7f19bb44b6da39bf8023be1b23e2022-12-21T19:51:54ZengFrontiers Media S.A.Frontiers in Immunology1664-32242021-11-011210.3389/fimmu.2021.695596695596IL-21 Rescues the Defect of IL-10-Producing Regulatory B Cells and Improves Allergic Asthma in DOCK8 Deficient MiceJinqiu Jiang0Jinqiu Jiang1Tao Qin2Liang Zhang3Qiao Liu4Jiabin Wu5Rongxin Dai6Rongxin Dai7Lina Zhou8Qin Zhao9Xiaoyan Luo10Hua Wang11Xiaodong Zhao12Xiaodong Zhao13Department of Dermatology, Ministry of Education Key Laboratory of Child Development and Disorders, National Clinical Research Center for Child Health and Disorders, China International Science and Technology Cooperation Base of Child Development and Critical Disorders, Children’s Hospital of Chongqing Medical University, Chongqing, ChinaChongqing Key Laboratory of Child Infection and Immunity, Children’s Hospital of Chongqing Medical University, Chongqing, ChinaDepartment of Infectious Diseases, Children’s Hospital of Chongqing Medical University, Chongqing, ChinaChongqing Key Laboratory of Child Infection and Immunity, Children’s Hospital of Chongqing Medical University, Chongqing, ChinaChongqing Key Laboratory of Child Infection and Immunity, Children’s Hospital of Chongqing Medical University, Chongqing, ChinaChongqing Key Laboratory of Child Infection and Immunity, Children’s Hospital of Chongqing Medical University, Chongqing, ChinaChongqing Key Laboratory of Child Infection and Immunity, Children’s Hospital of Chongqing Medical University, Chongqing, ChinaDepartment of Rheumatology and Immunology, Children’s Hospital of Chongqing Medical University, Chongqing, ChinaChongqing Key Laboratory of Child Infection and Immunity, Children’s Hospital of Chongqing Medical University, Chongqing, ChinaChongqing Key Laboratory of Child Infection and Immunity, Children’s Hospital of Chongqing Medical University, Chongqing, ChinaDepartment of Dermatology, Ministry of Education Key Laboratory of Child Development and Disorders, National Clinical Research Center for Child Health and Disorders, China International Science and Technology Cooperation Base of Child Development and Critical Disorders, Children’s Hospital of Chongqing Medical University, Chongqing, ChinaDepartment of Dermatology, Ministry of Education Key Laboratory of Child Development and Disorders, National Clinical Research Center for Child Health and Disorders, China International Science and Technology Cooperation Base of Child Development and Critical Disorders, Children’s Hospital of Chongqing Medical University, Chongqing, ChinaChongqing Key Laboratory of Child Infection and Immunity, Children’s Hospital of Chongqing Medical University, Chongqing, ChinaDepartment of Rheumatology and Immunology, Children’s Hospital of Chongqing Medical University, Chongqing, ChinaMutations in human DOCK8 cause a combined immunodeficiency syndrome characterized by allergic diseases such as asthma and food allergy. However, the underlying mechanism is unclear. Regulatory B (Breg) cells that produce IL-10 exert potent immunosuppressive functions in patients with allergic and autoimmune disorders. DOCK8-deficient B cells show diminished responses to TLR9 signaling, suggesting a possible defect in IL-10-producing Breg cells in those with DOCK8 deficiency, which may contribute to allergies. Here, we isolated peripheral blood mononuclear cells from DOCK8-deficient patients and generated a Dock8 KO mouse model to study the effect of DOCK8 deficiency on Breg cells. DOCK8-deficient patients and Dock8 KO mice harbored quantitative and qualitative defects in IL-10-producing Breg cells; these defects were caused by abnormal Dock8-/- CD4+ T cells. We found that recombinant murine (rm)IL-21 restored the function of Bregs both in vitro and in Dock8 KO mice, leading to reduced inflammatory cell infiltration of the lungs in a murine asthma model. Overall, the results provide new insight into the potential design of Breg-based or IL-21-based therapeutic strategies for allergic diseases, including asthma associated with DOCK8 deficiency.https://www.frontiersin.org/articles/10.3389/fimmu.2021.695596/fullregulatory B cellsIL-10DOCK8 deficiencyasthmaIL-21 |
| spellingShingle | Jinqiu Jiang Jinqiu Jiang Tao Qin Liang Zhang Qiao Liu Jiabin Wu Rongxin Dai Rongxin Dai Lina Zhou Qin Zhao Xiaoyan Luo Hua Wang Xiaodong Zhao Xiaodong Zhao IL-21 Rescues the Defect of IL-10-Producing Regulatory B Cells and Improves Allergic Asthma in DOCK8 Deficient Mice Frontiers in Immunology regulatory B cells IL-10 DOCK8 deficiency asthma IL-21 |
| title | IL-21 Rescues the Defect of IL-10-Producing Regulatory B Cells and Improves Allergic Asthma in DOCK8 Deficient Mice |
| title_full | IL-21 Rescues the Defect of IL-10-Producing Regulatory B Cells and Improves Allergic Asthma in DOCK8 Deficient Mice |
| title_fullStr | IL-21 Rescues the Defect of IL-10-Producing Regulatory B Cells and Improves Allergic Asthma in DOCK8 Deficient Mice |
| title_full_unstemmed | IL-21 Rescues the Defect of IL-10-Producing Regulatory B Cells and Improves Allergic Asthma in DOCK8 Deficient Mice |
| title_short | IL-21 Rescues the Defect of IL-10-Producing Regulatory B Cells and Improves Allergic Asthma in DOCK8 Deficient Mice |
| title_sort | il 21 rescues the defect of il 10 producing regulatory b cells and improves allergic asthma in dock8 deficient mice |
| topic | regulatory B cells IL-10 DOCK8 deficiency asthma IL-21 |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2021.695596/full |
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