6533b7ddfe1ef96bd1274040
RESEARCH PRODUCT
Human OX40 tunes the function of regulatory T cells in tumor and nontumor areas of hepatitis C virus-infected liver tissue.
Gianluca MenniniSilvia PiconeseMassimo SanchezG. GraziGuido AntonelliVincenzo BarnabaMassimo RossiIlenia PacellaClaudio TripodoEleonora TimperiStefania BrozzettiSimona Di FilippoKatia FazziMaria A Ntonietta LozziV. SchinzariNicola Guglielmosubject
MESH: Receptors OX40/metabolism*MESH: Interleukin-12/metabolismLiver CirrhosisMaleMacrophagemedicine.disease_causeMESH: Carcinoma Hepatocellular/immunology*T-Lymphocytes RegulatoryMESH: OX40 Ligand/metabolism0302 clinical medicineMESH: Aged 80 and overMESH: T-Lymphocytes Regulatory/physiology*MESH: Up-RegulationOX40MESH: AgedAged 80 and over0303 health scienceseducation.field_of_studyT REGMESH: Middle AgedMedicine (all)MESH: Liver Cirrhosis/immunology*Liver Neoplasmshemic and immune systemsMiddle AgedMESH: Liver Neoplasms/immunology*PhenotypeHepatitis CInterleukin-123. Good healthUp-RegulationPhenotypeLiver Neoplasm[SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/VirologyInterleukin 12[SDV.IMM]Life Sciences [q-bio]/ImmunologyFemalemedicine.symptomMESH: Hepatitis C/immunology*OX40; T REG; HEPATITIS C VIRUSHumanmedicine.medical_specialtyCarcinoma HepatocellularHepatitis C virusLiver CirrhosiPopulationInflammationchemical and pharmacologic phenomena[SDV.CAN]Life Sciences [q-bio]/CancerOX40 LigandBiologyMESH: PhenotypeMESH: Liver Neoplasms/virology03 medical and health sciencesIkaros Transcription FactorDownregulation and upregulationInternal medicinemedicineHumansMESH: Macrophages/metabolismeducation030304 developmental biologyAgedMESH: HumansHepatologyMacrophagesHEPATITIS C VIRUSMESH: Carcinoma Hepatocellular/virologyHepatologyReceptors OX40MESH: Ikaros Transcription Factor/metabolismMESH: Hepatitis C/complicationsMESH: MaleOX40 ligandImmunologyMESH: Liver Cirrhosis/virologyMESH: Female030215 immunologydescription
International audience; Regulatory T cells (Tregs) can be considered as a mixed population of distinct subsets, endowed with a diverse extent and quality of adaptation to microenvironmental signals. Here, we uncovered an opposite distribution of Treg expansion, phenotype, and plasticity in different microenvironments in the same organ (liver) derived from patients with chronic hepatitis C: On the one side, cirrhotic and tumor fragments were moderately and highly infiltrated by Tregs, respectively, expressing OX40 and a T-bet high IFN-c – " T-helper (Th)1-suppressing " phenotype; on the other side, noncirrhotic liver specimens contained low frequencies of Tregs that expressed low levels of OX40 and highly produced interferon-gamma (IFN-c; T-bet 1 IFN-c 1), thus becoming " Th1-like " cells. OX40-expressing and Th1-suppressing Tregs were enriched in the Helios-positive subset, carrying highly demethylated Treg cell-specific demethylated region that configures committed Tregs stably expressing forkhead box protein 3. OX40 ligand, mostly expressed by M2-like monocytes and macrophages, boosted OX40 1 Treg proliferation and antagonized the differentiation of Th1-like Tregs. However, this signal is counteracted in non-cirrhotic liver tissue (showing various levels of inflammation) by high availability of interleukin-12 and IFN-c, ultimately leading to complete, full Th1-like Treg differentiation. Conclusion: Our data demonstrate that Tregs can finely adapt, or even subvert, their classical inhibitory machinery in distinct microenvironments within the same organ. (HEPATOLOGY 2014;60:1494-1507)
| year | journal | country | edition | language |
|---|---|---|---|---|
| 2014-01-01 |