TY - JOUR
T1 - Migration of murine intestinal dendritic cell subsets upon intrinsic and extrinsic TLR3 stimulation
AU - Garcias López, Agnès
AU - Bekiaris, Vasileios
AU - Müller Luda, Katarzyna
AU - Hütter, Julia
AU - Ulmert, Isabel
AU - Getachew Muleta, Konjit
AU - Nakawesi, Joy
AU - Kotarsky, Knut
AU - Malissen, Bernard
AU - O'Keeffe, Meredith
AU - Holzmann, Bernhard
AU - Winston Agace, William
AU - Lahl, Katharina
PY - 2020/10/1
Y1 - 2020/10/1
N2 - Initiation of adaptive immunity to particulate antigens in lymph nodes largely depends on their presentation by migratory dendritic cells (DCs). DC subsets differ in their capacity to induce specific types of immunity, allowing subset-specific DC-targeting to influence vaccination and therapy outcomes. Faithful drug design, however, requires exact understanding of subset-specific versus global activation mechanisms. cDC1, the subset of DCs that excel in supporting immunity toward viruses, intracellular bacteria, and tumors, express uniquely high levels of the pattern recognition receptor TLR3. Using various murine genetic models, we show here that both, the cDC1 and cDC2 subsets of cDCs are activated and migrate equally well in response to TLR3 stimulation in a cell extrinsic and TNF-α dependent manner, but that cDC1 show a unique requirement for type I interferon signaling. Our findings reveal common and differing pathways regulating DC subset migration, offering important insights for the design of DC-based vaccination and therapy approaches.
AB - Initiation of adaptive immunity to particulate antigens in lymph nodes largely depends on their presentation by migratory dendritic cells (DCs). DC subsets differ in their capacity to induce specific types of immunity, allowing subset-specific DC-targeting to influence vaccination and therapy outcomes. Faithful drug design, however, requires exact understanding of subset-specific versus global activation mechanisms. cDC1, the subset of DCs that excel in supporting immunity toward viruses, intracellular bacteria, and tumors, express uniquely high levels of the pattern recognition receptor TLR3. Using various murine genetic models, we show here that both, the cDC1 and cDC2 subsets of cDCs are activated and migrate equally well in response to TLR3 stimulation in a cell extrinsic and TNF-α dependent manner, but that cDC1 show a unique requirement for type I interferon signaling. Our findings reveal common and differing pathways regulating DC subset migration, offering important insights for the design of DC-based vaccination and therapy approaches.
KW - Activation
KW - Dendritic cells
KW - Migration
KW - TLR3
KW - Type I interferon
U2 - 10.1002/eji.201948497
DO - 10.1002/eji.201948497
M3 - Journal article
C2 - 32383212
AN - SCOPUS:85085547883
SN - 0014-2980
VL - 50
SP - 1525
EP - 1536
JO - European Journal of Immunology
JF - European Journal of Immunology
IS - 10
ER -