title: Rejuvenation of mucosal immunosenescence by adipose tissue-derived mesenchymal stem cells.
abstract: Age-associated alterations in the mucosal immune system are generally termed mucosal immunosenescence. The major change seen in the aged mucosa is a failure to elicit an antigen-specific secretory IgA (SIgA) antibody response, which is a central player for host defense from various pathogens at mucosal surfaces. In this regard, it would be a first priority to compensate for mucosal dysregulation in the elderly in order to maintain their health in aging. We have successfully established antigen-specific SIgA antibody responses in aged (2 years old) mice, which provide protective immunity from Streptococcus pneumoniae and influenza virus infections, by using a new adjuvant system consisting of a plasmid encoding Flt3 ligand (pFL) and CpG ODN. In order to explore possible use of current mucosal vaccine strategies for the elderly, we have adoptively transferred adipose tissue-derived mesenchymal stem cells (AMSCs) to aged mice prior to mucosal vaccination. This immune therapy successfully resulted in protective antigen-specific antibody responses in the intestinal mucosa of aged mice that were comparable to those seen in young adult mice. In this regard, we postulate that adoptively transferred AMSCs could augment dendritic cell functions in aged mice. The potential cellular and molecular mechanisms whereby AMSCs restore mucosal immunity in immunosenescence are discussed in this short review. A stem cell transfer system could be an attractive and effective immunologic intervention strategy to reverse mucosal immunosenescence.
authors.affiliation: Department of Pediatric Dentistry, The University of Alabama at Birmingham, 1919 7th Avenue South, SDB 801 A1, Birmingham, AL 35294-0007, USA.
authors.forename: Akitoshi
authors.initials: A
authors.lastname: Tsuruhara
authors.affiliation: Department of Pediatric Dentistry, The University of Alabama at Birmingham, 1919 7th Avenue South, SDB 801 A1, Birmingham, AL 35294-0007, USA.|Department of Pediatrics, Graduate School of Medicine, Osaka City University, Asahi-cho 1-5-7, Abeno-ku, Osaka, Osaka 545-0051, Japan.
authors.forename: Kazuyoshi
authors.initials: K
authors.lastname: Aso
authors.affiliation: Department of Pediatrics, Graduate School of Medicine, Osaka City University, Asahi-cho 1-5-7, Abeno-ku, Osaka, Osaka 545-0051, Japan.
authors.forename: Daisuke
authors.initials: D
authors.lastname: Tokuhara
authors.affiliation: Department of Pediatric Dentistry, The University of Alabama at Birmingham, 1919 7th Avenue South, SDB 801 A1, Birmingham, AL 35294-0007, USA.|Department of Otolaryngology, Kagoshima University Faculty of Medicine, Sakuragaoka 8-35-1, Kagoshima, Kagoshima 890-8520, Japan.
authors.forename: Junichiro
authors.initials: J
authors.lastname: Ohori
authors.affiliation: Department of Pediatric Dentistry, The University of Alabama at Birmingham, 1919 7th Avenue South, SDB 801 A1, Birmingham, AL 35294-0007, USA.|Department of Otolaryngology, Kagoshima University Faculty of Medicine, Sakuragaoka 8-35-1, Kagoshima, Kagoshima 890-8520, Japan.
authors.forename: Masaki
authors.initials: M
authors.lastname: Kawabata
authors.affiliation: Department of Otolaryngology, Kagoshima University Faculty of Medicine, Sakuragaoka 8-35-1, Kagoshima, Kagoshima 890-8520, Japan.
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Kurono
authors.affiliation: Department of Pediatric Dentistry, The University of Alabama at Birmingham, 1919 7th Avenue South, SDB 801 A1, Birmingham, AL 35294-0007, USA.
authors.forename: Jerry R
authors.initials: JR
authors.lastname: McGhee
authors.affiliation: Department of Pediatric Dentistry, The University of Alabama at Birmingham, 1919 7th Avenue South, SDB 801 A1, Birmingham, AL 35294-0007, USA.
authors.forename: Kohtaro
authors.initials: K
authors.lastname: Fujihashi
mesh_terms: D000273:Adipose Tissue / Q000276:immunology*; D000375:Aging / Q000276:immunology* / Q000473:pathology; D000818:Animals; D006801:Humans; D018928:Immunity, Mucosal / Q000276:immunology*; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000276:immunology*; D051379:Mice; D011008:Pneumococcal Infections / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D013296:Streptococcus pneumoniae / Q000276:immunology*
keywords: aging; mucosa; secretory IgA; stem cells; vaccines