Phenotype and function of nasal dendritic cells

Abstract

Intranasal vaccination generates immunity across local, regional and distant sites. However, nasal dendritic cells (DC), pivotal for the induction of intranasal vaccine- induced immune responses, have not been studied in detail. Here, 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 FLT3 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 LPS 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-3hi 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.

Research Techniques Made Simple: Mass Cytometry Analysis Tools for Decrypting the Complexity of Biological Systems

“…The rigid connections established within the data representation structure (graph) may mislead the positioning of some cell nodes, possibly obscuring the underlying biology. Lee et al (2015) recently used CyTOF and SPADE to define in detail the phenotype and functional characteristics of distinct subsets of nasal dendritic cells in mice. SPADE clearly portrayed a map of the vast heterogeneity of nasal dendritic cells and identified new subsets that were not perceptible by manual gating on the basis of canonical marker expression.…”

Hydrogel nanoparticles and nanocomposites for nasal drug/vaccine delivery

“…Thus, the nose contains a large proportion of dendritic cells capable of managing and spreading immune responses (Lee et al 2015). In addition, mucosal vaccination has many advantages compared to parenteral pathway.…”

Mucosal Immune Response in Nasal-Associated Lymphoid Tissue upon Intranasal Administration by Adjuvants

“…NALT has a low frequency of CD103 + DCs, and CD11b + CD64 – F4/80 – DCs occupy the majority of DC subsets in NALT. By contrast, Peyer’s patches have a high frequency of CD103 + DCs [9]. Both CD103 + DCs in NALT and intestinal tracts are able to incorporate antigens and migrate to draining lymph nodes.…”

“…Although T cells of NALT show Th0-type dominant cytokine signature and are able to differentiate into Th1 or Th2 cells immediately after antigen inoculation by the nasal route [18], T cells in Peyer’s patches show memory phenotype [19]. DCs and macrophages are different between NALT and intestinal tracts (Table 1) [9, 20, 21]. NALT has a low frequency of CD103 + DCs, and CD11b + CD64 – F4/80 – DCs occupy the majority of DC subsets in NALT.…”

“…The NALT, which consists of T cells, B cells, dendritic cells (DCs), macrophages, and microfold cells, is located in the nasal cavity and is the first immune tissue exposed to inhalant antigens and pathogens [5, 9, 10]. Inhalant antigens are transported to the NALT by microfold cells located in the epithelium overlying the NALT and are taken up by DCs, resulting in their presentation to T cells [7].…”