Differential requirement for DOCK2 in migration of plasmacytoid dendritic cells versus myeloid dendritic cells.
The migratory properties of dendritic cells (DCs) are important for their functions. Although several chemokines and their receptors have been implicated in DC migration, the downstream signaling molecules are largely unknown. Here we show that DOCK2, a hematopoietic cell-specific CDM family protein, is indispensable for migration of plasmacytoid DCs (pDCs), but not myeloid DCs (mDCs). Although DOCK2-deficiency did not affect development of pDCs, DOCK2-deficient (DOCK2(-/-)) mice exhibited a severe reduction of pDCs in the spleen and lymph nodes. Adoptive transfer experiments revealed that DOCK2(-/-) pDCs failed to migrate into the periarteriolar lymphoid sheaths of the spleen. In DOCK2(-/-) pDCs, chemokine-induced Rac activation was severely impaired, resulting in the reduction of motility and the loss of polarity during chemotaxis. In contrast, DOCK2(-/-) mDCs did not show any defects in Rac activation and migration. These results indicate that pDCs and mDCs use distinct molecules to activate Rac during chemotaxis.
Gotoh
Kazuhito
K
Division of Immunogenetics, Department of Immunobiology and Neuroscience, Medical Institute of Bioregulation, Kyushu University, Fukuoka, Japan.
Tanaka
Yoshihiko
Y
Nishikimi
Akihiko
A
Inayoshi
Ayumi
A
Enjoji
Munechika
M
Takayanagi
Ryoichi
R
Sasazuki
Takehiko
T
Fukui
Yoshinori
Y
D000818:Animals; D002465:Cell Movement; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000166:cytology / Q000378:metabolism*; D020690:GTPase-Activating Proteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D020662:Guanine Nucleotide Exchange Factors; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D022423:Myeloid Cells / Q000166:cytology / Q000378:metabolism*
C471356:DOCK2 protein, mouse; D020690:GTPase-Activating Proteins; D020662:Guanine Nucleotide Exchange Factors