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 - 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 -