Highlights

In brief

Macrophages are immune cells involved in the detection and removal of bacteria and other harmful organisms. They differ in properties and behavior depending on their location in the body.

© Shutterstock

On the trail of two types of white blood cells

23 May 2019

Nerve bundles and blood vessels each have their own specific subtypes of macrophages.

People who grow up and reside in different countries typically end up developing different cultures and habits. The same could be said of immune cells in the body, which reside in different tissue ‘niches’.

Led by Florent Ginhoux of A*STAR's Singapore Immunology Network (SIgN), a team of scientists has discovered two distinct groups of interstitial macrophages (a type of white blood cell) that coexist and occupy specific compartments of tissues in the body.

“Macrophages are immune cells implicated in maintaining the normal functioning of tissues, from neuronal activity in the brain to the clearance of dying cells in all tissues,” Ginhoux explained, adding that macrophages differ in their properties and behavior depending on their location within tissue niches. His team thus sought to understand what those differences are and how those differences arise.

Using a technique called single-cell mRNA sequencing, the researchers observed that macrophages surrounding nerve bundles and those near blood vessels had different ‘signatures’, based on the genes they expressed and the proteins they displayed. Macrophages associated with blood vessels were characterized as Lyve1hiMHCIIlo, while those in close proximity to nerve bundles were characterized as Lyve1loMHCIIhi.

The researchers further demonstrated that Lyve1hiMHCIIlo macrophages were critical for maintaining blood vessel integrity, suppressing inflammation and reducing the extent to which collagen fibers are deposited in tissue. In mice whose Lyve1hiMHCIIlo macrophages had been removed, the team recorded increased blood vessel leakiness and worsened inflammation which delayed healing in the heart and lungs, ultimately resulting in greater scarring of the tissue.

On the other hand, Lyve1loMHCIIhi macrophages were more prone to interact with another subset of immune cells known as CD4+ T cells. Upon activation by the Lyve1loMHCIIhi macrophages, the CD4+ T cells increase in number and turn into regulatory T cells (Tregs), which are known to play a role in preventing autoimmune reactions.

Importantly, Ginhoux’s team found that both Lyve1hiMHCIIlo and Lyve1loMHCIIhi macrophages have a common origin—both are derived from immature cells called blood monocytes. “This in turn implies that the tissue microenvironment—either the blood vessels or nerve fibers—is the driver of monocyte-specific differentiation into either Lyve1hiMHCIIlo or Lyve1loMHCIIhi macrophages,” said Ginhoux.

Since nerve bundles and blood vessels are common ‘sub-tissue niches’ in many parts of the body, the two distinct macrophage populations likely play important roles in health and disease. Ginhoux and colleagues thus intend to explore more deeply how the two types of macrophages contribute to the development of cancer, for instance.

“We are also trying to better understand the role of nerve bundle-associated Lyve1loMHCIIhi macrophages. This subset of macrophages would be well placed to contribute to focal chemokine/cytokine gradients, which could promote tissue tolerance by modulating the activity of Tregs,” Ginhoux concluded.

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

Want to stay up to date with breakthroughs from A*STAR? Follow us on Twitter and LinkedIn!

References

Chakarov, S., Lim H. Y., Tan, L., Lim, S. Y., See, P., et al. Two distinct interstitial macrophage populations coexist across tissues in specific subtissular niches. Science 363, eaau0964 (2019). | article

About the Researcher

View articles

Florent Ginhoux

Senior Principal Investigator

Singapore Immunology Network (SIgN)
Florent Ginhoux is Senior Principal Investigator at the Singapore Immunology Network (SIgN), A*STAR. He obtained his PhD in 2004 from the University Pierre et Marie Curie, Paris VI. As a postdoctoral fellow, he joined the Laboratory of Miriam Merad in the Mount Sinai School of Medicine (MSSM), New York, where he studied the ontogeny and the homeostasis of cutaneous dendritic cell populations, with a strong focus on Langerhans cells and Microglia. In 2008, he became an Assistant Professor in the Department of Gene and Cell Medicine, MSSM and member of the Immunology Institute of MSSM. He joined SIgN in May 2009 as a Principal Investigator before becoming Senior Principal Investigator in 2017. He has been a Web of Science Highly Cited Researcher since 2016, and an EMBO member since 2022. Ginhoux is also an Adjunct Visiting Associate Professor in the Shanghai Immunology Institute, Jiao Tong University, as well as Adjunct Associate Professor in the Translational Immunology Institute, SingHealth and Duke NUS. He is now a laboratory director in Gustave Roussy Hospital, Villejuif, France. His new laboratory focuses on paediatric cancers.

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