Methods for the identification, targeting, isolation of human dendritic cell precursors and their use as biomarkers of inflammatory diseases

Ref: B0005

Research Institutes: Singapore Immunology Network (SIgN)

Tech readiness: Concept

Intellectual Property: Patent - Pending

Category: Healthcare - Diagnostics; Healthcare - Pharmaceuticals & Therapeutics

Author: Charis


Dendritic cells (DC) are professional antigen-presenting cells that orchestrate immune responses. The human DC population comprises two main functionally-specialized lineages, whose origins and differentiation pathways remain incompletely defined: plasmacytoid DC (pDC), and conventional DC (cDC), the latter comprising cDC1 and cDC2 sub-populations. Dissecting the origins and differentiation pathways giving rise to DC sub-populations is necessary to understand their homeostasis and role in immune responses, and for the development of DC subset-specific therapeutic interventions. In this investigation, we sought to understand and/or clarify if pDC are precursors of cDC or the conventionally-defined pDC population is heterogeneous, incorporating an independent pre-DC sub-population.

Our Innovation

Here we combine two high-dimensional technologies – massively-parallel single-cell mRNA sequencing (MARS-seq) and Cytometry by Time-of-Flight (CyTOF), to identify human blood CD123+CD33+-CD45RA+ DC precursors (pre-DC).  Pre-DC share surface markers with plasmacytoid DC (pDC) but have distinct functional properties that were previously attributed to pDC. Tracing the differentiation of DC from the bone marrow to the peripheral blood revealed that the pre-DC compartment contains distinct lineage-committed sub-populations including one early uncommitted CD123high pre-DC subset and two CD45RA+CD123low lineage-committed subsets exhibiting functional differences. The discovery of multiple committed pre-DC populations opens promising new avenues for the therapeutic exploitation of DC subset-specific targeting.

Potential Applications

Inflammatory and autoimmune diseases.

Our Value Proposition

Our technology proposes a cytometric gating strategy relating to the clear separation of pre-DCs, pDCs and cDC subsets for applications in inflammation and infection models through:-Identification of human pre-DC using markers CD169 and CD327; and/orDiagnosis or predictive progression of local or systemic inflammatory, autoimmune, infectious, metabolic diseases/conditions based on the detection of changes in pre-DC populations.Market Trends and OpportunitiesGlobal autoimmune diagnostics market worth was USD 11.88 billion in 2013 and is projected to reach USD 14.17 billion by 2020. Drivers of this market include the rise in the number of autoimmune disease cases worldwide and the significant increase in healthcare expenditure as a result of favorable government initiatives implemented to encourage diagnostics and research efforts in this field.
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