Abstract
Conventional and plasmacytoid dendritic cells (cDCs and pDCs) are the two populations of DCs that can be readily identified in human blood. Conventional DCs have been subdivided into CD1c+, or blood dendritic cells antigen (BDCA) 1 and CD141+, or BDCA-3, DCs, each having both unique gene expression profiles and functions. BDCA-3 DCs express high levels of toll-like receptor 3 and upon stimulation with Poly I:C secrete IFN-β, CXCL10, and IL-12p70. In this article, we show that activation of human BDCA-3 DCs with Poly I:C induces the expression of activation markers (CD40, CD80, and CD86) and immunoglobulin-like transcript (ILT) 3 and 4. This Poly I:C stimulation results in four populations identifiable by flow cytometry based on their expression of ILT3 and ILT4. We focused our efforts on profiling the ILT4− and ILT4+ DCs. These ILT-expressing BDCA-3 populations exhibit similar levels of activation as measured by CD40, CD80, and CD86; however, they exhibit differential cytokine secretion profiles, unique gene signatures, and vary in their ability to prime allogenic naïve T cells. Taken together, these data illustrate that within a pool of BDCA-3 DCs, there are cells poised to respond differently to a given input stimulus with unique output of immune functions.
Highlights
As key regulators of the immune system, antigen-presenting cells (APCs) play a primary role in acquiring, processing, and presenting both foreign and self-antigens to naïve CD4+ and CD8+ T cells, thereby initiating the adaptive branch of the immune system
Total blood dendritic cells (DCs) were enriched by negative selection, followed by flow cytometry sorting of the enriched DC fraction for plasmacytoid DCs (pDCs) (Lin−, CD123+, HLADR+), cDCs (Lin−, CD123−, HLADR+, CD1c+, CD11c+), and blood dendritic cells antigen (BDCA)-3 cDCs (Lin−, CD123−, HLADR+, CD1c−, CD141+) (Figure 1A)
Given that BDCA-3 cDCs expressed a limited repertoire of toll-like receptors (TLRs), we focused our initial efforts to characterize the BDCA-3 cDC response to Poly I:C, a TLR3 agonist
Summary
As key regulators of the immune system, antigen-presenting cells (APCs) play a primary role in acquiring, processing, and presenting both foreign and self-antigens to naïve CD4+ and CD8+ T cells, thereby initiating the adaptive branch of the immune system. Even though a variety of immunocytes, such as macrophages, monocytes, and B cells, are capable of functioning as APCs to a certain extent, dendritic cells (DCs) are considered the primary APCs for the stimulation of naïve T cells [1]. Three distinct subsets of DCs have been identified by their differential expression of three surface markers blood dendritic cells antigen (BDCA) 1, BDCA-2, and BDCA-3. BDCA-1 DC, or cDCs are characterized by their surface expression of Lin−, CD11c+, CD1c+, HLADR+, and CD123dim. BDCA-2 DCs, or pDCs, are identified by their surface markers Lin−, CD123+, CD4+, and HLADR+. The recently identified BDCA-3 cDCs are characterized as Lin−, CD123−, CD11c+, CD1c−, and by the unique expression of the chemokine receptor XCR1 [2, 3]. BDCA-1 DCs express toll-like receptors (TLRs) 2-6 and 9, while
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
