TY - JOUR
T1 - Bcl6-independent in vivo development of functional type 1 classical dendritic cells supporting tumor rejection
AU - Bagadia, Prachi
AU - O'Connor, Kevin W.
AU - Wu, Renee
AU - Ferris, Stephen T.
AU - Ward, Jeffrey P.
AU - Schreiber, Robert D.
AU - Murphy, Theresa L.
AU - Murphy, Kenneth M.
N1 - Funding Information:
This work was supported by the Howard Hughes Medical Institute (K.M.M.), the National Institutes of Health (NIH), National Institute of Allergy and Infectious Diseases (1RO1CA237088-01 to K.M.M.), and the National Science Foundation (DGE- 1745038 to P.B.). The Genome Technology Access Center in the Department of Genetics at Washington University School of Medicine is partially supported by National Cancer Institute (NCI) Cancer Center Support Grant P30 CA91842 to the Siteman Cancer Center and by the National Center for Research Resources (NCRR), a component of the NIH, Institute of Clinical and Translational Sciences/Clinical and Translational Sciences Award Grant UL1TR000448, and by the NIH Roadmap for Medical Research. This publication is solely the responsibility of the authors and does not necessarily represent the official view of NCRR or NIH. Tetramer preparation had the assistance of the Andrew M. and Jane M. Bursky Center for Human Immunology and Immunotherapy Programs, which supports the Immunomonitoring Laboratory, and the NCI of the NIH, which supports the Alvin J. Siteman Comprehensive Cancer Center with Cancer Center Support Grant P30CA91842, and the Washington University Rheumatic Diseases Research Resource-based Center Grant P30 AR073752.
Funding Information:
This work was supported by the Howard Hughes Medical Institute (K.M.M.), the National Institutes of Health (NIH), National Institute of Allergy and Infectious Diseases (1RO1CA237088-01 to K.M.M.), and the National Science Foundation (DGE-1745038 to P.B.). The Genome Technology Access Center in the Department of Genetics at Washington University School of Medicine is partially supported by National Cancer Institute (NCI) Cancer Center Support Grant P30 CA91842 to the Siteman Cancer Center and by the National Center for Research Resources (NCRR), a component of the NIH, Institute of Clinical and Translational Sciences/Clinical and Translational Sciences Award Grant UL1TR000448, and by the NIH Roadmap for Medical Research. This publication is solely the responsibility of the authors and does
Funding Information:
not necessarily represent the official view of NCRR or NIH. Tetramer preparation had the assistance of the Andrew M. and Jane M. Bursky Center for Human Immunology and Immunotherapy Programs, which supports the Immunomonitoring Laboratory, and the NCI of the NIH, which supports the Alvin J. Siteman Comprehensive Cancer Center with Cancer Center Support Grant P30CA91842, and the Washington University Rheumatic Diseases Research Resource–based Center Grant P30 AR073752.
Publisher Copyright:
Copyright © 2021 by The American Association of Immunologists, Inc.
PY - 2021/7/1
Y1 - 2021/7/1
N2 - The transcriptional repressor Bcl6 has been reported as required for development of a subset of classical dendritic cell (cDCs) called cDC1, which is responsible for cross-presentation. However, mechanisms and in vivo functional analysis have been lacking. We generated a system for conditional deletion of Bcl6 in mouse cDCs. We confirmed the reported in vitro requirement for Bcl6 in cDC1 development and the general role for Bcl6 in cDC development in competitive settings. However, deletion of Bcl6 did not abrogate the in vivo development of cDC1. Instead, Bcl6 deficiency caused only a selective reduction in CD8α expression by cDC1 without affecting XCR1 or CD24 expression. Normal cDC1 development was confirmed in Bcl6cKO mice by development of XCR1+ Zbtb46-GFP+ cDC1 by rejection of syngeneic tumors and by priming of tumor-specific CD8 T cells. In summary, Bcl6 regulates a subset of cDC1-specific markers and is required in vitro but not in vivo for cDC1 development.
AB - The transcriptional repressor Bcl6 has been reported as required for development of a subset of classical dendritic cell (cDCs) called cDC1, which is responsible for cross-presentation. However, mechanisms and in vivo functional analysis have been lacking. We generated a system for conditional deletion of Bcl6 in mouse cDCs. We confirmed the reported in vitro requirement for Bcl6 in cDC1 development and the general role for Bcl6 in cDC development in competitive settings. However, deletion of Bcl6 did not abrogate the in vivo development of cDC1. Instead, Bcl6 deficiency caused only a selective reduction in CD8α expression by cDC1 without affecting XCR1 or CD24 expression. Normal cDC1 development was confirmed in Bcl6cKO mice by development of XCR1+ Zbtb46-GFP+ cDC1 by rejection of syngeneic tumors and by priming of tumor-specific CD8 T cells. In summary, Bcl6 regulates a subset of cDC1-specific markers and is required in vitro but not in vivo for cDC1 development.
UR - http://www.scopus.com/inward/record.url?scp=85109016515&partnerID=8YFLogxK
U2 - 10.4049/jimmunol.1901010
DO - 10.4049/jimmunol.1901010
M3 - Article
C2 - 34135058
AN - SCOPUS:85109016515
SN - 0022-1767
VL - 207
SP - 125
EP - 132
JO - Journal of Immunology
JF - Journal of Immunology
IS - 1
ER -