Lee H, Ruane D, Law K, Ho Y, Garg A, Rahman A, Esterházy D, Cheong C, Goljo E, Sikora A G, Mucida D, Chen B K, Govindraj S, Breton G, Mehandru S
1] Division of Gastroenterology, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, New York, USA [2] Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
1] Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, New York, USA [2] Division of Infectious Diseases, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
Mucosal Immunol. 2015 Sep;8(5):1083-98. doi: 10.1038/mi.2014.135. Epub 2015 Feb 11.
Intranasal (i.n.) vaccination generates immunity across local, regional, and distant sites. However, nasal dendritic cells (DCs), pivotal for the induction of i.n. vaccine-induced immune responses, have not been studied in detail. Here, by using a variety of parameters, we define nasal DCs in mice and humans. Distinct subsets of "classical" DCs, dependent on the transcription factor zbtb46 were identified in the murine nose. The murine nasal DCs were Fms-related tyrosine 3 kinase ligand responsive and displayed unique phenotypic and functional characteristics, including the ability to present antigen, induce an allogeneic T-cell response, and migrate in response to lipopolysaccharide or live bacterial pathogens. Importantly, in a cohort of human volunteers, BDCA-1(+) DCs were observed to be the dominant nasal DC population at steady state. During chronic inflammation, the frequency of both BDCA-1(+) and BDCA-3(hi) DCs was reduced in the nasal tissue, associating the loss of these immune sentinels with chronic nasal inflammation. The present study is the first detailed description of the phenotypic, ontogenetic, and functional properties of nasal DCs, and will inform the design of preventative immunization strategies as well as therapeutic modalities against chronic rhinosinusitis.
鼻内（i.n.）接种疫苗可在局部、区域和远处部位产生免疫。然而，对于诱导鼻内疫苗免疫反应起关键作用的鼻内树突状细胞（DCs）尚未进行详细研究。在此，我们通过多种参数对小鼠和人类的鼻内DCs进行了定义。在小鼠鼻腔中鉴定出了依赖转录因子zbtb46的不同亚群的“经典”DCs。小鼠鼻内DCs对Fms相关酪氨酸3激酶配体有反应，并表现出独特的表型和功能特征，包括呈递抗原、诱导同种异体T细胞反应以及对脂多糖或活细菌病原体作出迁移反应的能力。重要的是，在一组人类志愿者中，观察到BDCA-1(+) DCs在稳态时是主要的鼻内DC群体。在慢性炎症期间，鼻组织中BDCA-1(+)和BDCA-3(hi) DCs的频率均降低，表明这些免疫哨兵的缺失与慢性鼻炎症有关。本研究首次详细描述了鼻内DCs的表型、个体发育和功能特性，将为预防性免疫策略以及针对慢性鼻窦炎的治疗方式的设计提供依据。
