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:10.1371/journal.pone.0060453

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

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Abstract

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.

Original language	English (US)
Article number	e60453
Journal	PloS one
Volume	8
Issue number	4
DOIs	https://doi.org/10.1371/journal.pone.0060453
State	Published - Apr 2 2013

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Fukuyama, Y., Tokuhara, D., Sekine, S., Aso, K., Kataoka, K., Davydova, J., Yamamoto, M., Gilbert, R. S., Tokuhara, Y., Fujihashi, K., Kunisawa, J., Yuki, Y., Kiyono, H., McGhee, J. R., & Fujihashi, K. (2013). Potential Roles of CCR5⁺ CCR6⁺ Dendritic Cells Induced by Nasal Ovalbumin plus Flt3 Ligand Expressing Adenovirus for Mucosal IgA Responses. PloS one, 8(4), Article e60453. https://doi.org/10.1371/journal.pone.0060453

Fukuyama, Y, Tokuhara, D, Sekine, S, Aso, K, Kataoka, K, Davydova, J , Yamamoto, M, Gilbert, RS, Tokuhara, Y, Fujihashi, K, Kunisawa, J, Yuki, Y, Kiyono, H, McGhee, JR & Fujihashi, K 2013, 'Potential Roles of CCR5⁺ CCR6⁺ Dendritic Cells Induced by Nasal Ovalbumin plus Flt3 Ligand Expressing Adenovirus for Mucosal IgA Responses', PloS one, vol. 8, no. 4, e60453. https://doi.org/10.1371/journal.pone.0060453

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abstract = "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.",

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AB - 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.

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Potential Roles of CCR5⁺ CCR6⁺ Dendritic Cells Induced by Nasal Ovalbumin plus Flt3 Ligand Expressing Adenovirus for Mucosal IgA Responses

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