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...
Guardado en:
| Autores principales: | , , , , , , , , , , |
|---|---|
| Formato: | article |
| Lenguaje: | EN |
| Publicado: |
Frontiers Media S.A.
2021
|
| Materias: | |
| Acceso en línea: | https://doaj.org/article/49b6f7f19bb44b6da39bf8023be1b23e |
| Etiquetas: |
Agregar Etiqueta
Sin Etiquetas, Sea el primero en etiquetar este registro!
|
| id |
oai:doaj.org-article:49b6f7f19bb44b6da39bf8023be1b23e |
|---|---|
| record_format |
dspace |
| spelling |
oai:doaj.org-article:49b6f7f19bb44b6da39bf8023be1b23e2021-11-15T06:06:22ZIL-21 Rescues the Defect of IL-10-Producing Regulatory B Cells and Improves Allergic Asthma in DOCK8 Deficient Mice1664-322410.3389/fimmu.2021.695596https://doaj.org/article/49b6f7f19bb44b6da39bf8023be1b23e2021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fimmu.2021.695596/fullhttps://doaj.org/toc/1664-3224Mutations 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.Jinqiu JiangJinqiu JiangTao QinLiang ZhangQiao LiuJiabin WuRongxin DaiRongxin DaiLina ZhouQin ZhaoXiaoyan LuoHua WangXiaodong ZhaoXiaodong ZhaoFrontiers Media S.A.articleregulatory B cellsIL-10DOCK8 deficiencyasthmaIL-21Immunologic diseases. AllergyRC581-607ENFrontiers in Immunology, Vol 12 (2021) |
| institution |
DOAJ |
| collection |
DOAJ |
| language |
EN |
| topic |
regulatory B cells IL-10 DOCK8 deficiency asthma IL-21 Immunologic diseases. Allergy RC581-607 |
| spellingShingle |
regulatory B cells IL-10 DOCK8 deficiency asthma IL-21 Immunologic diseases. Allergy RC581-607 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 |
| 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. |
| format |
article |
| 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 |
| title |
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_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_sort |
il-21 rescues the defect of il-10-producing regulatory b cells and improves allergic asthma in dock8 deficient mice |
| publisher |
Frontiers Media S.A. |
| publishDate |
2021 |
| url |
https://doaj.org/article/49b6f7f19bb44b6da39bf8023be1b23e |
| work_keys_str_mv |
AT jinqiujiang il21rescuesthedefectofil10producingregulatorybcellsandimprovesallergicasthmaindock8deficientmice AT jinqiujiang il21rescuesthedefectofil10producingregulatorybcellsandimprovesallergicasthmaindock8deficientmice AT taoqin il21rescuesthedefectofil10producingregulatorybcellsandimprovesallergicasthmaindock8deficientmice AT liangzhang il21rescuesthedefectofil10producingregulatorybcellsandimprovesallergicasthmaindock8deficientmice AT qiaoliu il21rescuesthedefectofil10producingregulatorybcellsandimprovesallergicasthmaindock8deficientmice AT jiabinwu il21rescuesthedefectofil10producingregulatorybcellsandimprovesallergicasthmaindock8deficientmice AT rongxindai il21rescuesthedefectofil10producingregulatorybcellsandimprovesallergicasthmaindock8deficientmice AT rongxindai il21rescuesthedefectofil10producingregulatorybcellsandimprovesallergicasthmaindock8deficientmice AT linazhou il21rescuesthedefectofil10producingregulatorybcellsandimprovesallergicasthmaindock8deficientmice AT qinzhao il21rescuesthedefectofil10producingregulatorybcellsandimprovesallergicasthmaindock8deficientmice AT xiaoyanluo il21rescuesthedefectofil10producingregulatorybcellsandimprovesallergicasthmaindock8deficientmice AT huawang il21rescuesthedefectofil10producingregulatorybcellsandimprovesallergicasthmaindock8deficientmice AT xiaodongzhao il21rescuesthedefectofil10producingregulatorybcellsandimprovesallergicasthmaindock8deficientmice AT xiaodongzhao il21rescuesthedefectofil10producingregulatorybcellsandimprovesallergicasthmaindock8deficientmice |
| _version_ |
1718428550108807168 |