期刊
ISCIENCE
卷 24, 期 11, 页码 -出版社
CELL PRESS
DOI: 10.1016/j.isci.2021.103225
关键词
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资金
- Canadian Institutes of Health Research [MOP114957, TCO125276, IBC-154053]
- National Institutes of Health (NIH) [R01AG054324]
- Canadian Foundation for Innovation (CFI)
- Universitede Montreal
- FRQ-S
The crosstalk between IECs and Th17-polarized CD4(+) T cells is crucial for mucosal homeostasis, with IL-17A acting in synergy with TNF to promote HIV trans-infection and outgrowth, while also inducing a pro-inflammatory and pro-viral molecular signature.
The crosstalk between intestinal epithelial cells (IECs) and Th17-polarized CD4(+) T cells is critical for mucosal homeostasis, with HIV-1 causing significant alterations in people living with HIV (PLWH) despite antiretroviral therapy (ART). In a model of IEC and T cell co-cultures, we investigated the effects of IL-17A, the Th17 hallmark cytokine, on IEC ability to promote de novo HIV infection and viral reservoir reactivation. Our results demonstrate that IL-17A acts in synergy with TNF to boost IEC production of CCL20, a Th17-attractant chemokine, and promote HIV trans-infection of CD4(+) T cells and viral outgrowth from reservoir cells of ART-treated PLWH. Importantly, the Illumina RNA-sequencing revealed an IL 17A-mediated pro-inflammatory and pro-viral molecular signature, including a decreased expression of type I interferon (IFN-I)-induced HIV restriction factors. These findings point to the deleterious features of IL-17A and raise awareness for caution when designing therapies aimed at restoring the paucity of mucosal Th17 cells in ART-treated PLWH.
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