The exact origin and precursor differentiation route of tissue macrophages remains controversial. At the 2024 congress of EULAR—The European Alliance of Associations for Rheumatology—new work sheds light on blood precursors of pathogenic tissue macrophages.
New work on precursors of inflammatory synovial macrophages sheds light on pathogenesis of rheumatoid arthritisRheumatoid arthritis is an autoimmune disease that causes joint inflammation and destruction. There is currently no cure—and although there are many treatments, their effectiveness varies from person to person, suggesting an undefined pathogenic diversity.
With this in mind, the group set out to discover whether quiescent human blood monocyte states are pre-committed to an inflammatory synovial transcriptional program. First, peripheral blood from healthy volunteers and RA patients with clinically well-controlled disease were enriched for monocytes by negative selection and subjected to single cell RNA sequencing.
All told, this work generated an exhaustive reference atlas comprising a total of 11 monocyte states across anatomical compartments relevant for RA. For example, it was possible to show that different clusters in fact represent the same inflammatory synovial macrophage subset, and are transcriptionally similar to an IL1B+ monocyte subset present in quiescent peripheral blood.
This work is important, because it not only defines a new monocyte cell taxonomy relevant for RA—with 11 continuous cell states that dynamically transition into each other across anatomical compartments—but also identifies potential blood precursors of pathogenic tissue macrophages.: New work on precursors of inflammatory synovial macrophages sheds light on pathogenesis of rheumatoid arthritis retrieved 13 June 2024 from https://medicalxpress.
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