CXCR5 Signals Fine-Tune Dendritic Cell Transcription and Regulate T2 Development.

BACKGROUND/OBJECTIVES: We previously demonstrated that dendritic cell (DC) expression of CXCR5 is required for T2 priming in mice infected with the helminth . In this manuscript we examined how CXCR5 controls DC mediated CD4 T helper 2 cell (T2) development.

METHODS

We used T2 priming assays, RNA-seq analyses and infection mouse models to identify roles for the CXCR5-expressing DCs in T2 development.

RESULTS

We showed that migratory conventional type 2 dendritic cells (cDC2) express CXCR5 and that deletion of prevents migratory DC priming of T2 cells while overexpression of CXCR5 enhances migratory DC priming of T2 cells . To understand how CXCR5 facilitates the T2 priming capabilities of migratory cDC2 cells, we performed RNAseq analysis on wildtype and DC subsets isolated from msLN of -infected mice. We observed that CXCR5 expression specifically by the migratory cDC2 subset promoted a pro-proliferative transcriptional program in cDC2 cells and was required for cDC2 cell accumulation in the msLN following infection. We demonstrated that CXCR5 expression specifically by cDC2 cells was necessary for upregulation of , which encodes a secreted protein (Chi3l1) that regulates allergic T2 responses. We showed that addition of recombinant Chi3l1 protein to T2 priming cultures enhanced T2 development and that deletion of specifically in DCs resulted in fewer cDC2 cells and decreased T2 development following infection.

CONCLUSIONS

CXCR5 expressed by cDC2 cells is required for induction of , which in turn promotes the T2 priming capacity of these DCs. These findings provide insight into the actions of CXCR5 and Chi3l1 in helminth infection.