Repression of the aryl-hydrocarbon receptor prevents oxidative stress and ferroptosis of intestinal intraepithelial lymphocytes

Dietary environmental factors shape the immune defence againstCryptosporidiuminfection

“…AHR expression and signalling is essential for both TCRab + and TCRgd + IEL survival, maintenance, and effector function (Dean et al, 2023;Li et al, 2011;Panda et al, 2023). In line with these findings, the percentage, and total numbers of natural CD8aa IELs recovered from naïve AHRKO immune mice were significantly lower compared with WT littermates whereas the numbers of TCRab + CD8ab + IELs were similar (Figure 4A-C).…”

“…While the exact mechanism by which these IELs sense epithelial injury during infection is unclear (Hoytema van , being in a constant state of heightened activation with increased cytolytic granzyme expression (Konjar et al, 2018) increases their ability to swiftly act on Cryptosporidiuminfected epithelial cells. The presence of IELs at the coalface of the mucosal barrier and their dependence on AHR (Dean et al, 2023;Li et al, 2011;Panda et al, 2023), opens up the possibility to modulate these IELs during Cryptosporidium infections through supplementation of dietary AHR ligands.…”

Ferroptosis Nanomedicine: Clinical Challenges and Opportunities for Modulating Tumor Metabolic and Immunological Landscape

“…Ferroptosis has captured widespread interest in oncology therapy due to their immense potential for direct tumor inhibition. ,− Interestingly, recent studies reveal that ferroptosis is strongly connected with T cell-mediated antitumor immunity, and the rational regulation of ferroptosis in TME holds potential to enhance the efficacy of many immunotherapeutic modalities. ,, However, it is worth mentioning that ferroptosis is a highly complex event and its impact on T cell mediated immune reactions is multifaceted, which warrants additional precautions when developing ferroptosis-dependent immunostimulatory strategies for tumor inhibition. At present, there are reported that ferroptosis can activate immunotherapy through its inherent immunogenic properties including antigen/DAMP release and secretion of pro-inflammatory cytokines, but may also exert an immunosuppressive effect on T cells through inducing T cell exhaustion and functional impairment (Figure ).…”

“…In addition to the utility of direct tumor cell inhibition, recent studies also demonstrate that ferroptosis is a substantial orchestrator to the tumor immune microenvironment, shedding light on valid strategies for modulating the tumor immune landscape to mount robust antitumor immunity. , Indeed, there is increasing evidence showing that ferroptosis in tumor cells and immune cells has crucial roles in shaping the tumor-immune interactions, which may impose both positive and negative impacts on the T cell-mediated antitumor immunity. For instance, a recent report by Zou et al showed that CD8 + T cells could induce tumor cell ferroptosis by reducing the expression of solute carrier family 3 member 2 (SLC3A2) and solute carrier family 7 member 11 (SLC7A11) in tumor cells to decrease the uptake of cystine, substantiating its contribution to cytotoxic T lymphocyte (CTL)-mediated tumor cell killing effect .…”

Bioluminescence imaging of Cyp1a1-luciferase reporter mice demonstrates prolonged activation of the aryl hydrocarbon receptor in the lung

“…In this setting, interactions between AHR and ligand stimulate Cyp1a1, Ahrr and TiParp expression that subsequently act to degrade AHR ligand, reduce AHR availability, and counter AHR activation. Failures in this selflimiting process that lead to a dysregulated AHR pathway are linked to disease pathology and increased cancer risk [20][21][22][23][24][25][26][27][28][29][30][31][32][33][34][35][36] .…”