Differential requirement for D0CK2 in migration of plasmacytoid dendritic cells versus myeloid dendritic cells

Kazuhito Gotoh, Yoshihiko Tanaka, Akihiko Nishikimi, Ayumi Inayoshi, Munechika Enjoji, Ryoichi Takayanagi, Takehiko Sasazuki, Yoshinori Fukui

Research output: Contribution to journalArticle

48 Citations (Scopus)

Abstract

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- 1) 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.

Original languageEnglish
Pages (from-to)2973-2976
Number of pages4
JournalBlood
Volume111
Issue number6
DOIs
Publication statusPublished - Mar 15 2008

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

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