TY - JOUR
T1 - Central role of conventional dendritic cells in regulation of bone marrow release and survival of neutrophils
AU - Jiao, Jingjing
AU - Dragomir, Ana Cristina
AU - Kocabayoglu, Peri
AU - Rahman, Adeeb H.
AU - Chow, Andrew
AU - Hashimoto, Daigo
AU - Leboeuf, Marylene
AU - Kraus, Thomas
AU - Moran, Thomas
AU - Carrasco-Avino, Gonzalo
AU - Friedman, Scott L.
AU - Merad, Miriam
AU - Aloman, Costica
PY - 2014/4/1
Y1 - 2014/4/1
N2 - Neutrophils are the most abundant cell type in the immune system and play an important role in the innate immune response. Using a diverse range of mouse models with either defective dendritic cell (DC) development or conditional DC depletion, we provide in vivo evidence indicating that conventional DCs play an important role in the regulation of neutrophil homeostasis. Flk2, Flt3L, and Batf3 knockout mice, which have defects in DC development, have increased numbers of liver neutrophils in the steady state. Conversely, neutrophil frequency is reduced in DC-specific PTEN knockout mice, which have an expansion of CD8+ and CD103+ DCs. In chimeric CD11c-DTR mice, conventional DC depletion results in a systemic increase of neutrophils in peripheral organs in the absence of histological inflammation or an increase in proinflammatory cytokines. This effect is also present in splenectomized chimeric CD11c-DTR mice and is absent in chimeric mice with 50% normal bone marrow. In chimeric CD11c-DTR mice, diphtheria toxin treatment results in enhanced neutrophil trafficking from the bone marrow into circulation and increased neutrophil recruitment. Moreover, there is an increased expression of chemokines/cytokines involved in neutrophil homeostasis and reduced neutrophil apoptosis. These data underscore the role of the DC pool in regulating the neutrophil compartment in nonlymphoid organs. The Journal of Immunology, 2014, 192: 3374-3382.
AB - Neutrophils are the most abundant cell type in the immune system and play an important role in the innate immune response. Using a diverse range of mouse models with either defective dendritic cell (DC) development or conditional DC depletion, we provide in vivo evidence indicating that conventional DCs play an important role in the regulation of neutrophil homeostasis. Flk2, Flt3L, and Batf3 knockout mice, which have defects in DC development, have increased numbers of liver neutrophils in the steady state. Conversely, neutrophil frequency is reduced in DC-specific PTEN knockout mice, which have an expansion of CD8+ and CD103+ DCs. In chimeric CD11c-DTR mice, conventional DC depletion results in a systemic increase of neutrophils in peripheral organs in the absence of histological inflammation or an increase in proinflammatory cytokines. This effect is also present in splenectomized chimeric CD11c-DTR mice and is absent in chimeric mice with 50% normal bone marrow. In chimeric CD11c-DTR mice, diphtheria toxin treatment results in enhanced neutrophil trafficking from the bone marrow into circulation and increased neutrophil recruitment. Moreover, there is an increased expression of chemokines/cytokines involved in neutrophil homeostasis and reduced neutrophil apoptosis. These data underscore the role of the DC pool in regulating the neutrophil compartment in nonlymphoid organs. The Journal of Immunology, 2014, 192: 3374-3382.
UR - http://www.scopus.com/inward/record.url?scp=84897490482&partnerID=8YFLogxK
U2 - 10.4049/jimmunol.1300237
DO - 10.4049/jimmunol.1300237
M3 - Article
C2 - 24591364
AN - SCOPUS:84897490482
SN - 0022-1767
VL - 192
SP - 3374
EP - 3382
JO - Journal of Immunology
JF - Journal of Immunology
IS - 7
ER -