Effect of JAK inhibitors Upadacitinib or Baricitinib on gene expression during human monocyte-derived macrophage differentiation

Macrophage phenotypic and functional heterogeneity derives from tissue-specific transcriptional signatures shaped by the local microenvironment. GM-CSF drives the generation of human monocyte-derived macrophages with a potent pro-inflammatory activity upon stimulation. Janus Kinase (JAK) inhibitors are small molecules that reversibly inhibit JAK activity and their subsequent intracellular signaling and have become the treatment of choice for diseases with an inflammatory or immune basis. We explored the molecular impact of blocking GM-CSFR-JAK2-STAT5 axis with the Janus Kinase (JAK) inhibitors Upadacitinib or Baricitinib on the gene expression profile in GM-CSF-primed human monocyte derived macrophages. mRNA profiles of human macrophages differentiated with GM-CSF (GM-MØ) from peripheral blood monocytes in the absence or in the presence of the Janus Kinase (JAK) inhibitors Upadacitinib or Baricitinib. Baricitinib (10nM) and Upadacitinib (10nM or 100nM) were added once-a-day during the 7-day differentiation procedure.