PMID- 20881208 OWN - NLM STAT- MEDLINE DCOM- 20110222 LR - 20210206 IS - 1528-0020 (Electronic) IS - 0006-4971 (Linking) VI - 116 IP - 26 DP - 2010 Dec 23 TI - Rho-mDia1 pathway is required for adhesion, migration, and T-cell stimulation in dendritic cells. PG - 5875-84 LID - 10.1182/blood-2010-01-264150 [doi] AB - 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. FAU - Tanizaki, Hideaki AU - Tanizaki H AD - Department of Dermatology, Kyoto University Graduate School of Medicine, Kyoto, Japan. FAU - Egawa, Gyohei AU - Egawa G FAU - Inaba, Kayo AU - Inaba K FAU - Honda, Tetsuya AU - Honda T FAU - Nakajima, Saeko AU - Nakajima S FAU - Moniaga, Catharina Sagita AU - Moniaga CS FAU - Otsuka, Atsushi AU - Otsuka A FAU - Ishizaki, Toshimasa AU - Ishizaki T FAU - Tomura, Michio AU - Tomura M FAU - Watanabe, Takeshi AU - Watanabe T FAU - Miyachi, Yoshiki AU - Miyachi Y FAU - Narumiya, Shuh AU - Narumiya S FAU - Okada, Takaharu AU - Okada T FAU - Kabashima, Kenji AU - Kabashima K LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20100929 PL - United States TA - Blood JT - Blood JID - 7603509 RN - 0 (Carrier Proteins) RN - 0 (Chemokine CCL21) RN - 0 (Diap1 protein, mouse) RN - 0 (Formins) RN - 0 (RNA, Messenger) RN - EC 3.6.5.2 (rho GTP-Binding Proteins) SB - IM MH - Animals MH - Blotting, Western MH - Carrier Proteins/*physiology MH - *Cell Adhesion MH - *Cell Movement MH - Chemokine CCL21/metabolism MH - Dendritic Cells/*immunology/metabolism MH - Enzyme-Linked Immunosorbent Assay MH - Female MH - Flow Cytometry MH - Formins MH - Lymph Nodes/immunology/metabolism/pathology MH - Lymphocyte Activation MH - Mice MH - Mice, Inbred BALB C MH - Mice, Inbred C57BL MH - Mice, Knockout MH - RNA, Messenger/genetics MH - Reverse Transcriptase Polymerase Chain Reaction MH - T-Lymphocytes/*immunology/*metabolism MH - rho GTP-Binding Proteins/genetics/*metabolism EDAT- 2010/10/01 06:00 MHDA- 2011/02/23 06:00 CRDT- 2010/10/01 06:00 PHST- 2010/10/01 06:00 [entrez] PHST- 2010/10/01 06:00 [pubmed] PHST- 2011/02/23 06:00 [medline] AID - S0006-4971(20)34792-3 [pii] AID - 10.1182/blood-2010-01-264150 [doi] PST - ppublish SO - Blood. 2010 Dec 23;116(26):5875-84. doi: 10.1182/blood-2010-01-264150. Epub 2010 Sep 29.