By tracing the lineage of different subtypes of immune cells, researchers are able to better understand how the body fights infection, or how autoimmune diseases arise.

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The rediscovered origin of an immune cell subtype

29 Nov 2019

By mapping the development trajectory of immune precursor cells, A*STAR scientists showed that plasmacytoid dendritic cells were incorrectly classified in the immune ‘family tree.’ 

A person’s history can reveal a lot about their character, skills and inclinations, and this information is often used by employers to assess candidates for a professional role. Analogously, the origins of immune cells give researchers and clinicians clues about how each type of immune cell functions in the body.

“If you want to understand how cells ‘work’ you need to understand how they develop to begin with,” said Florent Ginhoux, Senior Principal Investigator at the Singapore Immunology Network (SIgN).

Focusing on a group of immune cells known as dendritic cells (DCs), his team has discovered that two subtypes of DCs—plasmacytoid and conventional DCs— which were previously thought to be derived from a common progenitor, in fact arise from distinct lineages.

Plasmacytoid DCs are among the first cells to recognize pathogens and will immediately secrete molecules that not only alert other immune cells to clear the infection, but also directly kill pathogens and infected cells. Conventional DCs, in contrast, are more specialized in directly activating and priming T cells to orchestrate a very powerful and specific immune response.

Ginhoux’s team thoroughly mapped out the development trajectories of DCs using a combination of cell sorting, RNA sequencing and computational techniques. Their data revealed that a protein called Ly6D found on the surface of early lymphoid progenitors identifies cells that will give rise to plasmacytoid DCs and not to conventional DCs. The surface protein CD115 was also useful for classifying immune progenitors, especially the conventional DCs.

“We confirmed that CD115+ common DC progenitor cells follow a myeloid trajectory that we identified in our 2015 publication. On the other hand, CD115- progenitor cells, which were previously thought to be common DC progenitors, actually belong to a completely different family of immune cells—the lymphoid family,” Ginhoux explained, adding that these findings challenge researchers to re-evaluate the way the lymphoid family of immune cells is organized.

He emphasized that a thorough understanding of the developmental trajectories of conventional and plasmacytoid DCs will facilitate further immunological studies on initial responses to infections, autoimmune disorders and cancer.

“There are still a lot of open questions surrounding DCs with regards to their tissue-specificity, tissue-specific functions, activities during early life and aging, and so on. One of the main interests in the field is to exploit DC function, especially their antigen presentation capacity, as a target for novel vaccination and therapy strategies. Targeting DC progenitor cells could enhance those strategies,” he said.

The A*STAR-affiliated researchers contributing to this research are from the Singapore Immunology Network (SIgN).

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Dress, R. J., Dutertre, C. A., Giladi, A., Schlitzer, A., Low, I. et al. Plasmacytoid dendritic cells develop from Ly6D+ lymphoid progenitors distinct from the myeloid lineage. Nature Immunology 20(7), 852-864 (2019) | article

About the Researcher

Florent Ginhoux

Senior Principal Investigator

Singapore Immunology Network
Florent Ginhoux completed his undergraduate studies at the University Pierre et Marie Curie (UPMC), Paris VI. He subsequently obtained a Master’s degree from the Pasteur Institute in 2000 and his PhD from UPMC, Paris VI, in 2004. He is currently a Senior Principal Investigator at A*STAR’s Singapore Immunology Network (SIgN) and an EMBO Young Investigator. His laboratory focuses on the ontogeny and differentiation of macrophages and dendritic cells in both humans and mice. He was listed as a highly cited researcher on Web of Science in 2016, 2017 and 2018.

This article was made for A*STAR Research by Wildtype Media Group