Semaphorins guide the entry of dendritic cells into the lymphatics by activating myosin II.
The recirculation of leukocytes is essential for proper immune responses. However, the molecular mechanisms that regulate the entry of leukocytes into the lymphatics remain unclear. Here we show that plexin-A1, a principal receptor component for class III and class VI semaphorins, was crucially involved in the entry of dendritic cells (DCs) into the lymphatics. Additionally, we show that the semaphorin Sema3A, but not Sema6C or Sema6D, was required for DC transmigration and that Sema3A produced by the lymphatics promoted actomyosin contraction at the trailing edge of migrating DCs. Our findings not only demonstrate that semaphorin signals are involved in DC trafficking but also identify a previously unknown mechanism that induces actomyosin contraction as these cells pass through narrow gaps.
Department of Immunopathology, Research Institute for Microbial Diseases, Osaka University, Suita, Japan.
Hyota
H
Takamatsu
Noriko
N
Takegahara
Yukinobu
Y
Nakagawa
Michio
M
Tomura
Masahiko
M
Taniguchi
Roland H
RH
Friedel
Helen
H
Rayburn
Marc
M
Tessier-Lavigne
Yutaka
Y
Yoshida
Tatsusada
T
Okuno
Masayuki
M
Mizui
Sujin
S
Kang
Satoshi
S
Nojima
Tohru
T
Tsujimura
Yuji
Y
Nakatsuji
Ichiro
I
Katayama
Toshihiko
T
Toyofuku
Hitoshi
H
Kikutani
Atsushi
A
Kumanogoh
D000205:Actomyosin / Q000378:metabolism; D019264:Adoptive Transfer; D000818:Animals; D054441:Cell Migration Assays, Leukocyte; D002465:Cell Movement / Q000276:immunology; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D055879:Gene Knock-In Techniques; D007109:Immunity; D042601:Lymphatic Vessels / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D018345:Mice, Knockout; D009119:Muscle Contraction; D024462:Myosin Type II / Q000276:immunology / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D039942:Neuropilin-1 / Q000235:genetics; D011956:Receptors, Cell Surface / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D039961:Semaphorins / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D015398:Signal Transduction
D009419:Nerve Tissue Proteins; C492114:Plxna1 protein, mouse; D011956:Receptors, Cell Surface; D039961:Semaphorins; D039942:Neuropilin-1; D000205:Actomyosin; D024462:Myosin Type II