Aryl hydrocarbon receptor activation drives polymorphonuclear myeloid-derived suppressor cell response and efficiently attenuates experimental Sjögren’s syndrome

Myeloid-derived suppressor cells(MDSCs)comprise heterogeneous myeloid cell populations with immunosuppressive capacity that contribute to immune regulation and tolerance induction.We previously reported impaired MDSC function in patients with primary Sjögren’s syndrome(pSS)and mice with experimental SS(ESS).However,the molecular mechanisms underlying MDSC dysfunction remain largely unclear.In this study,we first found that aryl hydrocarbon receptor(AhR)was highly expressed by human and murine polymorphonuclear MDSCs(PMN-MDSCs).Indole-3-propionic acid(IPA),a natural AhR ligand produced from dietary tryptophan,significantly promoted PMN-MDSC differentiation and suppressive function on CD4^(+)T cells.In contrast,feeding a tryptophan-free diet resulted in a decreased PMN-MDSC response,a phenotype that could be reversed by IPA supplementation.The functional importance of PMN-MDSCs was demonstrated in ESS mice by using a cell-depletion approach.Notably,AhR expression was reduced in PMN-MDSCs during ESS development,while AhR antagonism resulted in exacerbated ESS pathology and dysregulated T effector cells,which could be phenocopied by a tryptophan-free diet.Interferon regulatory factor 4(IRF4),a repressive transcription factor,was upregulated in PMN-MDSCs during ESS progression.Chromatin immunoprecipitation analysis revealed that IRF4 could bind to the promoter region of AhR,while IRF4 deficiency markedly enhanced AhR-mediated PMN-MDSC responses.Furthermore,dietary supplementation with IPA markedly ameliorated salivary glandular pathology in ESS mice with restored MDSC immunosuppressive function.Together,our results identify a novel function of AhR in modulating the PMN-MDSC response and demonstrate the therapeutic potential of targeting AhR for the treatment of pSS.

Flake channels construction of hydroxyapatite/gelatin cryogel with excellent flame retardant properties for enhancing the capturing of iodine

Safe and efficient capturing of volatile radioiodine is of extremely important significance in the treatment of spent fuel.Herein,the flake channels in gelatin-hydroxyapatite(HAP@Ge)cryogel with excellent flame retardant properties were constructed by immobilizing hydroxyapatite nanorods(HAP)on Gelatin(Ge)cryogel for enhancing the capturing of iodine.The immobilization of HAP nanorods enhanced thermal stability,provided low rates of dynamic heat transfer and dissipation,and remarkably improved the flame retardant and smoke suppression properties of the Ge cryogel,which can effectively prevent the occurrence of safety incidents caused by further thermal degradation or combustion of this cryogel.More importantly,it was effective in improving the rapid enrichment of iodine,resulting in a high adsorption capacity.The maximum adsorption capacity of HAP@Ge cryogel for iodine vapor reached 2693 mg/g at equilibrium.The high adsorption capacity for iodine was attributed to the multi-scale porous structure in HAP@Ge cryogel,which offered effective channels for iodine diffusion,whereas the numerous complex and irregular flakes provided sufficient number of active sites for iodine capture.The adsorption process was chemical in nature and involved the-PO_(4)^(3-),-OH,-C=O,and-NHR groups on HAP@Ge cryogel.Moreover,the complex porous structure of HAP@Ge cryogel enhanced the physical capturing of iodine.These advantages,such as low-cost raw material,simple preparation method,good flame retardancy,and excellent capturing performance for iodine indicated that HAP@Ge cryogel is a potential candidate for the removal of radioactive iodine in the exhaust gas stream of post-treatment plants.