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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.

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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).

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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

Florent Ginhoux

Senior Principal Investigator

Singapore Immunology Network
Florent Ginhoux graduated in Biochemistry from the University Pierre et Marie CURIE (UPMC), Paris VI, obtained a Masters degree in Immunology from the Pasteur Institute in 2000 and his PhD in 2004 from UPMC, Paris VI. As a postdoctoral fellow, he joined the Laboratory of Miriam Merad in the Mount Sinai School of Medicine (MSSM), New York. 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 the Singapore Immunology Network (SIgN), A*STAR in May 2009 as a Junior Principal Investigator. He is now a Senior Principal Investigator and an EMBO Young Investigator and his laboratory is focusing 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. Ginhoux holds the following adjunct positions: Adjunct Assistant Professor, NUS, Singapore; Adjunct Assistant Professor, Duke-NUS, Singapore; Joint Scientist, KKH, Singapore; Adjunct Senior Principal Investigator, IMB, A*STAR, Singapore and Adjunct Visiting Associate Professor, Shanghai Institute of Immunology at Shanghai Jiao Tong University School of Medicine, China.

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