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Paper Reading Liver-Resident NK Cells Control Antiviral Activity of Hepatic T Cells via the PD-1-PD-L1 Axis Jing Zhou, Hui Peng, Kun Li, ..., Haiming Wei, Rui Sun, Zhigang Tian Immunity, 2018 Recently, researchers have identified a unique subset of NK cells enriched in the murine liver, which were described as CD49a+ CD49b-liver-resident NK (LrNK) cells. LrNK cells and conventional NK (cNK) cells exhibit significant differences in terms of phenotype, gene expression profile, and roles in contact hypersensitivity. Moreover, compared with cNK cells, LrNK cells require different transcription factors and progenitor origins for their development. CD49a+CD49b- LrNK cells from wild-type (WT) mice at steady state highly expressed T-bet, CD200R, and tumor necrosis factor (TNF)-related apoptosis-inducing ligand(TRAIL) but lack edeomesodermin (Eomes) expression. In contrast, CD49a-CD49b+ cNK cells were Eomes positive with nearly undetectable expression of CD200R and TRAIL. Analysis of genome-wide transcriptional profiles of LrNK and liver cNK cells indicate that genes involved in negative regulation of the immune response were enriched in LrNK cells compared with cNK cells including Lag3, PD-L2, TRAIL, PD-L1, and CD39. Furthermore, during acute (Armstrong) and chronic (Clone13) LCMV infection, LrNK cells proliferated more vigorously than cNK cells and represented a phenotypically stable lineage during homeostasis and MCMV infection. Then the authors found that LrNK cells effectively restrain T cell responses during viral infection, whereas cNK cells have the opposite effect. Flow-cytometry analysis revealed there were no differences regarding cytokine secretion or cyto-toxic molecule release by the total NK cell population between Rag1-/-Tbx21-/- and control mice upon virus challenge while expression of PD-L1 increased on LrNK cells at day 7 after LCMV and adenovirus infection. Furthermore, the inhibitory role of LrNK cells was mediated by cell-cell contact and not by soluble factors, as evidenced by Transwell assays. This indicated that LrNK cells directly regulate T cell responses. Additionally, blockade of PD-L1 in the coculture system restored T cell proliferation in the presence of LrNK cells demonstrated that LrNK cells directly suppress T cell responses via the engagement of the PD-L1 checkpoint.  https:///10.1016/j.immuni.2018.12.024 Treg-Cell Control of a CXCL5-IL-17 Inflammatory Axis Promotes Hair-Follicle-Stem-Cell Differentiation During Skin-Barrier Repair Anubhav N. Mathur, Bahar Zirak, Ian C. Boothby, ..., Abul K. Abbas, Niwa Ali, Michael D. Rosenblum Immunity, 2019 Restoration of barrier-tissue integrity after injury is dependent on the function of immune cells and stem cells (SCs) residing in the tissue. In this paper, the authors demonstrated that Treg cells play a vital role in restoring skin-barrier integrity after epidermal injury. Treg cells in skin facilitate HFSC differentiation during hair regeneration. In this relatively non-inflammatory context, Treg cells promote ‘‘classical’’ HFSC differentiation toward hair-follicle keratinocyte lineages, at least in part, through direct interactions with HFSCs. In contrast to hair-follicle cycling, epidermal injury is highly inflammatory. In this paper, the authors found that neutralization of CXCL5 and IL-17A and neutrophil depletion partially restored barrier function and Lgr5-derived cell migration into the interfollicular epidermis (IFE) in the absence of Treg cells which indicated that in this context, Treg cells regulated a specific inflammatory module mediated by CXCL5 and promoted HFSC differentiation toward IFE keratinocytes.  https:///10.1016/j.immuni.2019.02.013 Edited by Feng Xie |
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