TY - JOUR
T1 - Distinct progenitor lineages contribute to the heterogeneity of plasmacytoid dendritic cells
AU - Rodrigues, Patrick Fernandes
AU - Alberti-Servera, Llucia
AU - Eremin, Anna
AU - Grajales-Reyes, Gary E.
AU - Ivanek, Robert
AU - Tussiwand, Roxane
N1 - Funding Information:
We thank A. G. Rolink (DBM University of Basel), K. M. Murphy (Washington University in St. Louis), and P. Tsapogas (DBM University of Basel) for sharing reagents, expertise and discussions; B. Lambrecht and M. Guilliams (VIB-UGent Center for Inflammation Research) for sharing data and reagents; M. Busslinger (Research Institute of Molecular Pathology IMP, Vienna) for kindly providing us with Ebf1hCD2 reporter mice; D. Schreiner and C. King for constant input and critical reading of the manuscript; D. Labes (DBM University of Basel), K. Eschbach and C. Beisel (Department of Biosystems Science and Engineering (D-BSSE) University of Zurich, Basel) for excellent technical support; the DBM-Microscopy Core Facility; A. Brülhart and all the animal caretakers of WRO1060; and C. Cannavo for IT support. This study was supported by SNF project number PP00P3_150714 and by the Novartis Foundation for medical-biological research n.16A052. This work is dedicated to the memory of Ton Rolink.
Publisher Copyright:
© 2018 The Author(s).
PY - 2018/7/1
Y1 - 2018/7/1
N2 - Plasmacytoid dendritic cells (pDCs) are an immune subset devoted to the production of high amounts of type 1 interferons in response to viral infections. Whereas conventional dendritic cells (cDCs) originate mostly from a common dendritic cell progenitor (CDP), pDCs have been shown to develop from both CDPs and common lymphoid progenitors. Here, we found that pDCs developed predominantly from IL-7R + lymphoid progenitor cells. Expression of SiglecH and Ly6D defined pDC lineage commitment along the lymphoid branch. Transcriptional characterization of SiglecH + Ly6D + precursors indicated that pDC development requires high expression of the transcription factor IRF8, whereas pDC identity relies on TCF4. RNA sequencing of IL-7R + lymphoid and CDP-derived pDCs mirrored the heterogeneity of mature pDCs observed in single-cell analysis. Both mature pDC subsets are able to secrete type 1 interferons, but only myeloid-derived pDCs share with cDCs their ability to process and present antigen.
AB - Plasmacytoid dendritic cells (pDCs) are an immune subset devoted to the production of high amounts of type 1 interferons in response to viral infections. Whereas conventional dendritic cells (cDCs) originate mostly from a common dendritic cell progenitor (CDP), pDCs have been shown to develop from both CDPs and common lymphoid progenitors. Here, we found that pDCs developed predominantly from IL-7R + lymphoid progenitor cells. Expression of SiglecH and Ly6D defined pDC lineage commitment along the lymphoid branch. Transcriptional characterization of SiglecH + Ly6D + precursors indicated that pDC development requires high expression of the transcription factor IRF8, whereas pDC identity relies on TCF4. RNA sequencing of IL-7R + lymphoid and CDP-derived pDCs mirrored the heterogeneity of mature pDCs observed in single-cell analysis. Both mature pDC subsets are able to secrete type 1 interferons, but only myeloid-derived pDCs share with cDCs their ability to process and present antigen.
UR - http://www.scopus.com/inward/record.url?scp=85048703337&partnerID=8YFLogxK
U2 - 10.1038/s41590-018-0136-9
DO - 10.1038/s41590-018-0136-9
M3 - Article
C2 - 29925996
AN - SCOPUS:85048703337
SN - 1529-2908
VL - 19
SP - 711
EP - 722
JO - Nature immunology
JF - Nature immunology
IS - 7
ER -