摘要：SummaryThe 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 promotede novoHIV 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 HIVtrans-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.Graphical abstractDisplay OmittedHighlights•IL-17A acts in synergy with TNF to enhance CCL20 production in IEC exposed to HIV•IL-17A/TNF-activated IEC efficiently promote HIVtrans-infection of CD4+T cells•IL-17A reprograms IEC to boost HIV outgrowth from CD4+T cells of ART-treated PLWH•IL-17A decreases the expression of IFN-I-induced HIV restriction factors in IECImmunology; Immune response; Virology
