By Samantha Black, Ph.D.

September 4, 2019 -- New research confirms the existence of two new subpopulations interstitial macrophages (IM), which are crucial to the pulmonary immune system. Published in Nature Communications on August 3, researchers from the Immunophysiology Laboratory of the GIGA Institute at the University of Liege provide insights into the characterization of these IM.

The pulmonary immune system is one of the body’s first lines of defense against invaders, whether they are harmless or not. Sometimes dysfunction of the immune system occurs when it responds against harmless compounds, as is the case in the development of asthma. More than 25 million Americans have asthma according to the Asthma and Allergy Foundation of America. Research suggests that IM could help prevent the development of asthma, serving as therapeutic targets.

Using single-cell RNA-sequencing (scRNA-seq), researchers identified two subsets of IM in mouse models: CD206+ IM and CD206− IM. Using confocal microscopy, it was determined that the two subpopulations differ in their localization within the lung, with CD206+ IM prefentially found in the bronchial interstitium and CD206− IM primarily located in the alveolar interstitium. Functionally, CD206+ IM had upregulated transcripts associated with positive regulation of leukocyte chemotaxis, response to wounding and receptor-mediated endocytosis, consistent with their phenotype and lysosomal vacuoles. These cells secrete high levels of chemokines and immunoregulatory cytokines. CD206 – IM were associated with increased expression for antigen processing and presentation, regulation of T cell activation and defense response. CD206 -IM are involved in responding to inflammatory signals and pathogen recognition. These functions were determined using Gene Ontology enrichment analysis and proteome profiling. The evidence provided by this research study confirms the existence of two unique subpopulations of IM in the lung.

The researchers also confirmed the half-life, self-maintenance potential, and localization at steady-state, as well as their stimulus-dependent regulation in an inflammatory context of cells in these two IM populations. Preventing the development of asthma and other chronic respiratory diseases is an important goal. Considering and classifying unique immune cell types will be crucial for determining therapeutic targets against immune-mediated respiratory diseases.

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