The differentiation and maintenance of RORγt+ Tregs respectively require integrin β8 expression by dendritic cells and commensal microbiota

【作者】 陈正涛； 王美祥； 刘位秀； 陈君兰； 王丁丁； 宋文刚； 唐华；

【机构】 泰山医学院； 复旦大学附属公共卫生临床中心； 武汉大学；

【摘要】 Backgroud: In early life, Change or absence of the symbiotic microbiota can lead to exacerbated type 2 immunity and allergic inflammations. Recent researches demonstrate that RORγt+ regulatory T cells(Tregs) regulate type 2 immune respond. The generation of it is dependent on dendritic cells and microbiota, but mechanisms are poorly understood. Methods: BM recipients were irradiated with two doses of 550 rads 3 h apart, and received 2 × 106 Zbtb46-DTR BMcells by intravenous injection.Results: DC lack of intgrin β8 resulted in loss of RORγt+ Tregs in the SI lamina propria(SILP). Loss of DCs in SILP of z DC-DTR bone marrow chimeras after treated with DT for 7 days did not influence the generation of RORγ+ Tregs. The frequencies of RORγt+ and Ki67+ RORγt+ pTregs were decreased in SILP of C57 mice after treated with antibiotics for 7 days and increased after remove antibiotics for 7 days. Oral SCFA in water help to improve the proliferation of RORγt+ p Treg subsets in SILP after treated with antibiotics. Conclusion: Integrin β8 expressed in SILP DCs play a critical role in the induction and microbiota in the gut act as a key factor on maintenance of RORγt+ pTregs.更多还原

【Abstract】 Backgroud: In early life, Change or absence of the symbiotic microbiota can lead to exacerbated type 2 immunity and allergic inflammations. Recent researches demonstrate that RORγt+ regulatory T cells(Tregs) regulate type 2 immune respond. The generation of it is dependent on dendritic cells and microbiota, but mechanisms are poorly understood. Methods: BM recipients were irradiated with two doses of 550 rads 3 h apart, and received 2 × 106 Zbtb46-DTR BMcells by intravenous injection.Results: DC lack of intgrin β8 resulted in loss of RORγt+ Tregs in the SI lamina propria(SILP). Loss of DCs in SILP of z DC-DTR bone marrow chimeras after treated with DT for 7 days did not influence the generation of RORγ+ Tregs. The frequencies of RORγt+ and Ki67+ RORγt+ pTregs were decreased in SILP of C57 mice after treated with antibiotics for 7 days and increased after remove antibiotics for 7 days. Oral SCFA in water help to improve the proliferation of RORγt+ p Treg subsets in SILP after treated with antibiotics. Conclusion: Integrin β8 expressed in SILP DCs play a critical role in the induction and microbiota in the gut act as a key factor on maintenance of RORγt+ pTregs.更多还原