RationaleInflammatory monocyte (MC) subset polarization is a hallmark of systemic and tissue inflammatory feature in diabetes. The underlying molecular mechanism remains unclear.Methods and resultsBlood pro-inflammatory Ly6Chigh and anti-inflammatory Ly6Clow MC subsets were isolated from control (C57/BL6), type 1 diabetes mellitus (T1DM), and type 2 diabetes mellitus (T2DM) mice by flow cytometry sorting and subjected to bulk high-throughput RNA-sequencing.
Intensive and integrative functional bioinformatic studies were performed by analyzing the transcriptome through seven pairs of comparison between Ly6Chigh and Ly6Clow MC subsets and between different mouse groups. We examined molecular features of three key immune activation signals in innate and adaptive immune responses, including signal 1 antigen (Ag)-presenting, signal 2 immune checkpoint, and signal 3 cytokine, and their upstream transcription factors (TF).
A total of 10 differentially expressed genes (DEG) of MHC-II molecules (signal 1) presented a low expression profile in Ly6Chigh MCs from all mice and mostly further reduced in T2DM Ly6Chigh MC. Ly6Chigh MCs show high intercellular inflammatory propagation based on immune checkpoint/cytokine-ligand expression but low intracellular inflammatory capacity based on immune checkpoint/cytokine-receptor expression, both further enhanced in T1/T2DM.
Frontiers in Immunology published a clinical update in Infectious Disease on 08 May 2026.
The item focuses on Empowered pro-inflammatory features in Ly6C monocytes and altered antigen-presenting capacity in Ly6Chigh monocytes in diabetic mice.
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