title: Retinoic acid treated human dendritic cells induce T regulatory cells via the expression of CD141 and GARP which is impaired with age.
abstract: Aged subjects display increased susceptibility to mucosal diseases. Retinoic Acid (RA) plays a major role in inducing tolerance in the mucosa. RA acts on Dendritic cells (DCs) to induce mucosal tolerance. Here we compared the response of DCs from aged and young individuals to RA with a view to understand the role of DCs in age-associated increased susceptibility to mucosal diseases. Our investigations revealed that compared to young DCs, RA stimulated DCs from aged subjects are defective in inducing IL-10 and T regulatory cells. Examinations of the underlying mechanisms indicated that RA exposure led to the upregulation of CD141 and GARP on DCs which rendered the DCs tolerogenic. CD141(hi), GARP(+) DCs displayed enhanced capacity to induce T regulatory cells compared to CD141(lo) and GARP(-) DCs. Unlike RA stimulated DCs from young, DCs from aged subjects exhibited diminished upregulation of both CD141 and GARP. The percentage of DCs expressing CD141 and GARP on RA treatment was significantly reduced in DCs from aged individuals. Furthermore, the remaining CD141(hi), GARP(+) DCs from aged individuals were also deficient in inducing T regs. In summary, reduced response of aged DCs to RA enhances mucosal inflammation in the elderly, increasing their susceptibility to mucosal diseases.
authors.affiliation: Division of Basic and Clinical Immunology, Department of Medicine, University of California, Irvine, CA 92697, USA.
authors.forename: Sudhanshu
authors.initials: S
authors.lastname: Agrawal
authors.affiliation: Division of Basic and Clinical Immunology, Department of Medicine, University of California, Irvine, CA 92697, USA.
authors.forename: Sreerupa
authors.initials: S
authors.lastname: Ganguly
authors.affiliation: Division of Basic and Clinical Immunology, Department of Medicine, University of California, Irvine, CA 92697, USA.
authors.forename: Alexander
authors.initials: A
authors.lastname: Tran
authors.affiliation: Division of Basic and Clinical Immunology, Department of Medicine, University of California, Irvine, CA 92697, USA.
authors.forename: Padmaja
authors.initials: P
authors.lastname: Sundaram
authors.affiliation: Division of Basic and Clinical Immunology, Department of Medicine, University of California, Irvine, CA 92697, USA.
authors.forename: Anshu
authors.initials: A
authors.lastname: Agrawal
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000378:metabolism*; D000954:Antigens, Surface / Q000378:metabolism*; D003713:Dendritic Cells / Q000187:drug effects* / Q000378:metabolism; D005260:Female; D006801:Humans; D016753:Interleukin-10 / Q000378:metabolism; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism*; D008875:Middle Aged; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects* / Q000378:metabolism; D018180:Thrombomodulin; D014212:Tretinoin / Q000494:pharmacology*; D055815:Young Adult
chemical_list: D000954:Antigens, Surface; C508609:IL10 protein, human; C087215:LRRC32 protein, human; D008565:Membrane Proteins; C546931:THBD protein, human; D018180:Thrombomodulin; D016753:Interleukin-10; D014212:Tretinoin
keywords: GARP; T regulatory cells; aging; dendritic cells; retinoic acid