Deciphering the fate of slan⁺ -monocytes in human tonsils by gene expression profiling

Monocytic cells perform crucial homeostatic and defensive functions. However, their fate and characterization at the transcriptomic level in human tissues are partially understood, often as a consequence of the lack of specific markers allowing their unequivocal identification. The 6-sulfo LacNAc (slan) antigen identifies a subset of non-classical (NC) monocytes in the bloodstream, namely the slan⁺ -monocytes. In recent studies, we and other groups have reported that, in tonsils, slan marks dendritic cell (DC)-like cells, as defined by morphological, phenotypical, and functional criteria. However, subsequent investigations in lymphomas have uncovered a significant heterogeneity of tumor-infiltrating slan⁺ -cells, including a macrophage-like state. Based on their emerging role in tissue inflammation and cancer, herein we investigated slan⁺ -cell fate in tonsils by using a molecular-based approach. Hence, RNA from tonsil slan⁺ -cells, conventional CD1c⁺ DCs (cDC2) and CD11b⁺ CD14⁺ -macrophages was subjected to gene expression analysis. For comparison, transcriptomes were also obtained from blood cDC2, classical (CL), intermediate (INT), NC, and slan⁺ -monocytes. Data demonstrate that the main trajectory of human slan⁺ -monocytes infiltrating the tonsil tissue is toward a macrophage-like population, displaying molecular features distinct from those of tonsil CD11b⁺ CD14⁺ -macrophages and cDC2. These findings provide a novel view on the terminal differentiation path of slan⁺ -monocytes, which is relevant for inflammatory diseases and lymphomas.