Plasmacytoid dendritic cells are short-lived: reappraising the influence of migration, genetic factors and activation on estimation of lifespan.
Plasmacytoid dendritic cells (pDCs) play an important role in immunity to certain pathogens and immunopathology in some autoimmune diseases. They are thought to have a longer lifespan than conventional DCs (cDCs), largely based on a slower rate of BrdU labeling by splenic pDCs. Here we demonstrated that pDC expansion and therefore BrdU labeling by pDCs occurs in bone marrow (BM). The rate of labeling was similar between BM pDCs and spleen cDCs. Therefore, slower BrdU labeling of spleen pDCs likely reflects the "migration time" (∼2 days) for BrdU labeled pDCs to traffic to the spleen, not necessarily reflecting longer life span. Tracking the decay of differentiated DCs showed that splenic pDCs and cDCs decayed at a similar rate. We suggest that spleen pDCs have a shorter in vivo lifespan than estimated utilizing some of the previous approaches. Nevertheless, pDC lifespan varies between mouse strains. pDCs from lupus-prone NZB mice survived longer than C57BL/6 pDCs. We also demonstrated that activation either positively or negatively impacted on the survival of pDCs via different cell-death mechanisms. Thus, pDCs are also short-lived. However, the pDC lifespan is regulated by genetic and environmental factors that may have pathological consequence.
The Walter &Eliza Hall Institute of Medical Research, Parkville, 3052, Australia.|Department of Medical Biology, University of Melbourne, Parkville, 3010, Australia.
Yifan
Y
Zhan
The Walter &Eliza Hall Institute of Medical Research, Parkville, 3052, Australia.|Department of Medical Biology, University of Melbourne, Parkville, 3010, Australia.|Department of Nephrology, Royal Melbourne Hospital, Parkville, 3050, Australia.
Kevin V
KV
Chow
The Walter &Eliza Hall Institute of Medical Research, Parkville, 3052, Australia.
Priscilla
P
Soo
The Walter &Eliza Hall Institute of Medical Research, Parkville, 3052, Australia.|Department of Medical Biology, University of Melbourne, Parkville, 3010, Australia.
Zhen
Z
Xu
The Walter &Eliza Hall Institute of Medical Research, Parkville, 3052, Australia.|Department of Medical Biology, University of Melbourne, Parkville, 3010, Australia.
Jamie L
JL
Brady
The Walter &Eliza Hall Institute of Medical Research, Parkville, 3052, Australia.|Department of Medical Biology, University of Melbourne, Parkville, 3010, Australia.
Kate E
KE
Lawlor
The Walter &Eliza Hall Institute of Medical Research, Parkville, 3052, Australia.|Department of Medical Biology, University of Melbourne, Parkville, 3010, Australia.
Seth L
SL
Masters
Monash Biomedicine Discovery Institute, Department of Biochemistry and Molecular Biology, Monash University, Clayton VIC 3168, Australia.
Meredith
M
O'keeffe
The Walter &Eliza Hall Institute of Medical Research, Parkville, 3052, Australia.|Department of Medical Biology, University of Melbourne, Parkville, 3010, Australia.
Ken
K
Shortman
The Walter &Eliza Hall Institute of Medical Research, Parkville, 3052, Australia.|Department of Medical Biology, University of Melbourne, Parkville, 3010, Australia.
Jian-Guo
JG
Zhang
The Walter &Eliza Hall Institute of Medical Research, Parkville, 3052, Australia.|Department of Medical Biology, University of Melbourne, Parkville, 3010, Australia.|Department of Microbiology &Immunology, University of Melbourne, Parkville, 3010, Australia.
Andrew M
AM
Lew
D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology* / Q000378:metabolism; D001973:Bromodeoxyuridine / Q000378:metabolism; D002454:Cell Differentiation; D002465:Cell Movement; D002470:Cell Survival; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000166:cytology* / Q000378:metabolism; D051379:Mice; D013154:Spleen / Q000166:cytology* / Q000378:metabolism
D001973:Bromodeoxyuridine