CXCR4 cell surface expression is critical for the homing of T regulatory (Treg) cells to the bone marrow (BM). We hypothesize that CXCR4 enrichment on Tregs cell surface may abbreviate their transit time to reach BM. Umbilical cord-blood CD25 Tregs underwent CXCR4 dual enrichment and expansion using the CRANE process to generate CXCR4-enriched Tregs (Treg) cells, which showed a faster migration across the Transwell membrane toward CXCL12/stromal cell-derived factor 1α (SDF1α) at 15, 30, and 60 min, when compared to unmanipulated Treg cells ( < 0.0001). Treg exhibited preferential homing to BM at 12 and 24 h. Metacluster analysis of BM showed a decrease in CD8 and an increase in CD39 and CD73 and CXCR5 when compared to Treg. Treg decreased plasma TGF-β1/β2 and IFN-γ levels. When compared to control, Treg cells decreased in CD8 T cell, IFN-γ, and TNF-α expression in BM. We conclude that Treg show enhanced migration toward CXCL12/SDF1α and a preferential homing to BM resulting in resolution of inflammation.
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| http://dx.doi.org/10.1016/j.isci.2024.110830 | DOI Listing |
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