Conventional dendritic cells (cDCs) are continuously replenished by bone marrow‐derived precursors called pre‐DCs, which traffic through the blood to peripheral tissues. Pre‐DCs are a heterogeneous ...population that includes cDC subset‐committed progenitors, namely pre‐cDC1 and pre‐cDC2, which give rise to mature cDC1 and cDC2, respectively. Regulation of pre‐DC subset trafficking is thought to aid the host response to immune challenge. However, the molecular cues regulating pre‐cDC1 versus pre‐cDC2 trafficking toward peripheral sites during homeostasis and disease remain elusive. Here, we report that pre‐cDC1 but not pre‐cDC2 express the T helper type 1‐associated chemokine receptor CXCR3. Moreover, we identify a cell‐intrinsic role for CXCR3 in the trafficking of pre‐cDC1 to melanoma tumors but not to non‐inflamed organs. We also show that tumor cDC1 numbers can be increased pharmacologically by targeting dipeptidyl peptidase‐4 (CD26), a negative regulator of CXCR3 ligands. Our findings demonstrate that pre‐cDC1 trafficking is regulated distinctly from pre‐cDC2, which is relevant for our understanding of the DC lineage in the context of cancer and inflammation.
The migration of conventional dendritic cell (cDC) precursors (pre‐DCs) is required for anti‐cancer immunity. The two subsets of cDC, cDC1 and cDC2, derive from committed progenitors called pre‐cDC1 and pre‐cDC2, respectively. In this study, we describe the differential expression of chemokine receptors by pre‐DC subsets and show that pre‐cDC1 but not pre‐cDC2 use CXCR3 to traffic into melanoma tumors in mice. We further show that the number of cDC1 within tumors can be increased through pharmacological inhibition of dipeptidyl‐peptidase 4 (DPP4), which normally inactivates the CXCR3 ligands CXCL9 and CXCL10.
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.