Rho-mDia1 pathway is required for adhesion, migration, and T-cell stimulation in dendritic cells.
Dendritic cells (DCs) are essential for the initiation of acquired immune responses through antigen acquisition, migration, maturation, and T-cell stimulation. One of the critical mechanisms in this response is the process actin nucleation and polymerization, which is mediated by several groups of proteins, including mammalian Diaphanous-related formins (mDia). However, the role of mDia in DCs remains unknown. Herein, we examined the role of mDia1 (one of the isoforms of mDia) in DCs. Although the proliferation and maturation of bone marrow-derived DCs were comparable between control C57BL/6 and mDia1-deficient (mDia1(-/-)) mice, adhesion and spreading to cellular matrix were impaired in mDia1(-/-) bone marrow-derived DCs. In addition, fluorescein isothiocyanate-induced cutaneous DC migration to draining lymph nodes in vivo and invasive migration and directional migration to CCL21 in vitro were suppressed in mDia1(-/-) DCs. Moreover, sustained T-cell interaction and T-cell stimulation in lymph nodes were impaired by mDia1 deficiency. Consistent with this, the DC-dependent delayed hypersensitivity response was attenuated by mDia1-deficient DCs. These results suggest that actin polymerization, which is mediated by mDia1, is essential for several aspects of DC-initiated acquired immune responses.
Tanizaki
Hideaki
H
Department of Dermatology, Kyoto University Graduate School of Medicine, Kyoto, Japan.
Egawa
Gyohei
G
Inaba
Kayo
K
Honda
Tetsuya
T
Nakajima
Saeko
S
Moniaga
Catharina Sagita
CS
Otsuka
Atsushi
A
Ishizaki
Toshimasa
T
Tomura
Michio
M
Watanabe
Takeshi
T
Miyachi
Yoshiki
Y
Narumiya
Shuh
S
Okada
Takaharu
T
Kabashima
Kenji
K
D000818:Animals; D015153:Blotting, Western; D002352:Carrier Proteins / Q000502:physiology*; D002448:Cell Adhesion; D002465:Cell Movement; D054421:Chemokine CCL21 / Q000378:metabolism; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005434:Flow Cytometry; D000080865:Formins; D008198:Lymph Nodes / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D008213:Lymphocyte Activation; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D012333:RNA, Messenger / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism*; D020741:rho GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism*
D002352:Carrier Proteins; D054421:Chemokine CCL21; C491464:Diap1 protein, mouse; D000080865:Formins; D012333:RNA, Messenger; D020741:rho GTP-Binding Proteins