Differential chemokine receptor expression and usage by pre‐ cDC cDC 1 and pre‐ cDC cDC 2

摘要

Abstract Conventional dendritic cells ( cDC s) are continuously replenished by bone marrow‐derived precursors called pre‐ DC s, which traffic through the blood to peripheral tissues. Pre‐ DC s are a heterogeneous population that includes cDC subset‐committed progenitors, namely pre‐ cDC 1 and pre‐ cDC 2, which give rise to mature cDC 1 and cDC 2, respectively. Regulation of pre‐DC subset trafficking is thought to aid the host response to immune challenge. However, the molecular cues regulating pre‐ cDC 1 versus pre‐ cDC 2 trafficking toward peripheral sites during homeostasis and disease remain elusive. Here, we report that pre‐ cDC 1 but not pre‐ cDC 2 express the T helper type 1‐associated chemokine receptor CXCR 3. Moreover, we identify a cell‐intrinsic role for CXCR 3 in the trafficking of pre‐ cDC 1 to melanoma tumors but not to non‐inflamed organs. We also show that tumor cDC 1 numbers can be increased pharmacologically by targeting dipeptidyl peptidase‐4 ( CD 26), a negative regulator of CXCR 3 ligands. Our findings demonstrate that pre‐ cDC 1 trafficking is regulated distinctly from pre‐ cDC 2, which is relevant for our understanding of the DC lineage in the context of cancer and inflammation.