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

Potential roles of CCR5(+) CCR6(+) dendritic cells induced by nasal ovalbumin plus Flt3 ligand expressing adenovirus for mucosal IgA responses.
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DOI:
10.1371/journal.pone.0060453
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发表时间:
2013
期刊:
影响因子:
3.7
通讯作者:
Fujihashi K
Fujihashi K
中科院分区:
综合性期刊3区
文献类型:
--
作者:
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

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我们评估了CCR 5 +/CCR 6 +/CD 11b +/CD 11 c+树突状细胞(DCs)在粘膜免疫后诱导卵清蛋白(OVA)特异性抗体(Ab)应答中的作用。给予小鼠鼻内OVA加表达Flt 3配体的腺病毒(Ad-FL)显示出鼻咽相关淋巴组织(NALT)和颈部淋巴结(CLN)中CCR 5 +/CCR 6 +/CD 11b +/CD 11 c + DC的早期扩增。随后,该DC亚群响应于这些组织中产生的高水平CCR配体而驻留在下颌下腺(SMG)和鼻通道(NP)中。CCR 5 −/−和CCR 6 −/−小鼠中CD 11b +/CD 11 c + DCs均显著减少。用来自CD 11 c-白喉毒素受体(CD 11 c-DTR)和CCR 5 −/−或CD 11 c-DTR和CCR 6 −/−小鼠的骨髓细胞重建的嵌合体小鼠,经鼻给予OVA加Ad-FL后,血浆IgG升高,但唾液和鼻洗液中的伊加降低以及抗OVA分泌型伊加(SIgA)Ab应答降低。这些结果表明,CCR 5 + CCR 6 + DC在诱导Ag特异性SIgA抗体应答中起重要作用。
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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