Phenotype and functions of conventional dendritic cells are not compromised in aged mice.
Aging has profound effects on the immune system, including thymic involution, reduced diversity of the T cell receptor repertoire, reduced effector T cell and B cell function and chronic increase of proinflammatory cytokine production by innate immune cells. The precise effects of aging on conventional dendritic cells (cDC), the main antigen presenting cells of the immune system, however, are not well understood. We found that in aged mice the number of cDC in the spleen and lymph nodes remained stable, whereas the number of cDC in the lungs increased with age. Whereas cDC in mice showed similar cycling kinetics in all organs tested, cDC reconstitution by aged bone marrow precursors was relatively higher than that of their young counterparts. With the exception of CD86, young and aged cDC did not differ in their expression of co-stimulatory molecules at steady state. Most toll-like receptor (TLR) ligands induced comparable upregulation of co-stimulatory molecules CD40, CD86 and B7H1 on young and aged cDC, whereas TLR2 and TLR5 stimulation resulted in reduced upregulation of CD80 and CD86 on aged cDC in vitro. In vivo, influenza infection-induced upregulation of CD86, but not other co-stimulatory molecules, was lower in aged DC. Young and aged DC were equally capable of direct and cross presentation of antigens in vitro. Transcriptome analysis did not reveal any significant difference between young and aged cDC. These data show that unlike T and B cells, the maintenance of cDC throughout the life of a healthy animal is relatively robust during the aging process.
Immune Imaging Program, The Centenary Institute for Cancer Medicine and Cell Biology, Newtown, New South Wales, Australia.
Sioh-Yang
SY
Tan
Lois L
LL
Cavanagh
William
W
d'Advigor
Nick
N
Shackel
Barbara
B
Fazekas de St Groth
Wolfgang
W
Weninger
D000375:Aging / Q000276:immunology*; D000818:Animals; D017951:Antigen Presentation / Q000276:immunology; D051940:B7-2 Antigen / Q000276:immunology* / Q000378:metabolism; D060890:B7-H1 Antigen / Q000276:immunology* / Q000378:metabolism; D001854:Bone Marrow Cells / Q000276:immunology / Q000378:metabolism; D019013:CD40 Antigens / Q000276:immunology* / Q000378:metabolism; D002452:Cell Count; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism / Q000821:virology; D005260:Female; D005434:Flow Cytometry; D016130:Immunophenotyping; D009980:Influenza A virus / Q000276:immunology; D055666:Lipopeptides / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000494:pharmacology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D020411:Oligonucleotide Array Sequence Analysis; D009976:Orthomyxoviridae Infections / Q000276:immunology / Q000821:virology; D013154:Spleen / Q000276:immunology / Q000378:metabolism; D051193:Toll-Like Receptors / Q000819:agonists / Q000276:immunology / Q000378:metabolism; D059467:Transcriptome / Q000235:genetics / Q000276:immunology; D015854:Up-Regulation / Q000187:drug effects
D051940:B7-2 Antigen; D060890:B7-H1 Antigen; D019013:CD40 Antigens; D055666:Lipopeptides; D008070:Lipopolysaccharides; C508075:Pam(3)CSK(4) peptide; D051193:Toll-Like Receptors