PLoS ONE (Jan 2013)

Potential roles of CCR5(+) CCR6(+) dendritic cells induced by nasal ovalbumin plus Flt3 ligand expressing adenovirus for mucosal IgA responses.

  • Yoshiko Fukuyama,
  • Daisuke Tokuhara,
  • Shinichi Sekine,
  • Kazuyoshi Aso,
  • Kosuke Kataoka,
  • Julia Davydova,
  • Masato Yamamoto,
  • Rebekah S Gilbert,
  • Yuka Tokuhara,
  • Keiko Fujihashi,
  • Jun Kunisawa,
  • Yoshikazu Yuki,
  • Hiroshi Kiyono,
  • Jerry R McGhee,
  • Kohtaro Fujihashi

DOI
https://doi.org/10.1371/journal.pone.0060453
Journal volume & issue
Vol. 8, no. 4
p. e60453

Abstract

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We assessed the role of CCR5(+)/CCR6(+)/CD11b(+)/CD11c(+) dendritic cells (DCs) for induction of ovalbumin (OVA)-specific antibody (Ab) responses following mucosal immunization. Mice given nasal OVA plus an adenovirus expressing Flt3 ligand (Ad-FL) showed early expansion of CCR5(+)/CCR6(+)/CD11b(+)/CD11c(+) DCs in nasopharyngeal-associated lymphoid tissue (NALT) and cervical lymph nodes (CLNs). Subsequently, this DC subset became resident in submandibular glands (SMGs) and nasal passages (NPs) in response to high levels of CCR-ligands produced in these tissues. CD11b(+)/CD11c(+) DCs were markedly decreased in both CCR5(-/-) and CCR6(-/-) mice. Chimera mice reconstituted with bone marrow cells from CD11c-diphtheria toxin receptor (CD11c-DTR) and CCR5(-/-) or CD11c-DTR and CCR6(-/-) mice given nasal OVA plus Ad-FL had elevated plasma IgG, but reduced IgA as well as low anti-OVA secretory IgA (SIgA )Ab responses in saliva and nasal washes. These results suggest that CCR5(+)CCR6(+) DCs play an important role in the induction of Ag-specific SIgA Ab responses.