期刊
JOURNAL OF EXPERIMENTAL MEDICINE
卷 215, 期 7, 页码 1823-1838出版社
ROCKEFELLER UNIV PRESS
DOI: 10.1084/jem.20171704
关键词
-
资金
- Arnold and Mabel Beckman Foundation Beckman Young Investigator Award
- Burroughs Wellcome Fund Investigators in the Pathogenesis of Infectious Disease award
- National Institutes of Health [R01 AI113118, 5T32AI007163]
- Burroughs Wellcome Fund Career Award for Medical Scientists
- National Science Foundation Graduate Research Fellowship [DGE-1143954]
- McDonnell International Scholars Academy at Washington University in St. Louis
- National Institute of Medical General Sciences Cell and Molecular Biology Training grant [GM007067]
- National Center for Research Resources-National Institutes of Health
- National Institute of Neurological Disorders and Stroke [N01NS02331]
- Washington University in St. Louis Institute of Clinical and Translational Sciences grant from the National Center for Advancing Translational Sciences of the National Institutes of Health [UL1 TR000448]
The cytokine IL-10 antagonizes pathways that control Mycobacterium tuberculosis (Mtb) infection. Nevertheless, the impact of IL-10 during Mtb infection has been difficult to decipher because loss-of-function studies in animal models have yielded only mild phenotypes. We have discovered that the transcription factor basic helix-loop-helix family member e40 (Bhlhe40) is required to repress Il10 expression during Mtb infection. Loss of Bhlhe40 in mice results in higher Il10 expression, higher bacterial burden, and early susceptibility similar to that observed in mice lacking IFN-gamma. Deletion of Il10 in Bhlhe40(-/-) mice reverses these phenotypes. Bhlhe40 deletion in T cells or CD11c(+) cells is sufficient to cause susceptibility to Mtb. Bhlhe40 represents the first transcription factor found to be essential during Mtb infection to specifically regulate Il10 expression, revealing the importance of strict control of IL-10 production by innate and adaptive immune cells during infection. Our findings uncover a previously elusive but significant role for IL-10 in Mtb pathogenesis.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据