TY - JOUR
T1 - Differential requirements for DOCK2 and phosphoinositide-3-kinase γ during T and B lymphocyte homing
AU - Nombela-Arrieta, César
AU - Lacalle, Rosa Ana
AU - Montoya, María C.
AU - Kunisaki, Yuya
AU - Megías, Diego
AU - Marqués, Miriam
AU - Carrera, Ana C.
AU - Mañes, Santos
AU - Fukui, Yoshinori
AU - Martínez-A, Carlos
AU - Stein, Jens V.
N1 - Funding Information:
We are grateful to Matthias Wymann and Emilio Hirsch for providing PI3Kγ-deficient animals, Tatsuo Kinashi for the GST-RalGDS RBD construct, and José Luis Zugaza for helpful discussion. We also thank Cathy Mark for outstanding secretarial assistance and our animal facility staff, Teresa de la Cueva, Lucio Gómez and Pilar Pallares, for excellent animal care. C.N.-A. received a fellowship from the Spanish Council for Scientific Research (CSIC). J.V.S. was supported by a Human Frontiers Science Program fellowship and is currently supported by a Ramon y Cajal contract from the Spanish Ministry of Science and Technology. The Department of Immunology and Oncology was founded and is supported by the CSIC and Pfizer. Part of this work was supported by EU grant QLRT-2000-02171.
PY - 2004/9
Y1 - 2004/9
N2 - Chemokines guide lymphocytes from blood to secondary lymphoid organs by triggering integrin-dependent firm adhesion under vascular flow and directed migration of T and B lymphocytes within lymphoid tissue. Here, we analyze the roles of DOCK2, a mammalian homolog of Caenorhabditis elegans CED-5 and Drosophila melanogaster Myoblast City, and phosphoinositide-3-kinase (PI3K) during lymphocyte recirculation. DOCK2 mediated efficient lymphocyte migration in a largely PI3K-independent manner, although a minor, PI3K-dependent pathway for migration was observed in wild-type and DOCK2-deficient lymphocytes. In T cells, this residual migration depended mainly on PI3Kγ, whereas other PI3K isoforms were implicated in B cells. In vitro adhesion assays and intravital microscopy of lymphoid organ vasculature uncovered an unexpected defect in integrin activation in DOCK2-/- B cells, whereas lack of DOCK2 did not affect chemokine-triggered integrin activation in T cells. DOCK2 and PI3Kγ thus play distinct roles during T and B cell integrin activation and migration.
AB - Chemokines guide lymphocytes from blood to secondary lymphoid organs by triggering integrin-dependent firm adhesion under vascular flow and directed migration of T and B lymphocytes within lymphoid tissue. Here, we analyze the roles of DOCK2, a mammalian homolog of Caenorhabditis elegans CED-5 and Drosophila melanogaster Myoblast City, and phosphoinositide-3-kinase (PI3K) during lymphocyte recirculation. DOCK2 mediated efficient lymphocyte migration in a largely PI3K-independent manner, although a minor, PI3K-dependent pathway for migration was observed in wild-type and DOCK2-deficient lymphocytes. In T cells, this residual migration depended mainly on PI3Kγ, whereas other PI3K isoforms were implicated in B cells. In vitro adhesion assays and intravital microscopy of lymphoid organ vasculature uncovered an unexpected defect in integrin activation in DOCK2-/- B cells, whereas lack of DOCK2 did not affect chemokine-triggered integrin activation in T cells. DOCK2 and PI3Kγ thus play distinct roles during T and B cell integrin activation and migration.
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U2 - 10.1016/j.immuni.2004.07.012
DO - 10.1016/j.immuni.2004.07.012
M3 - Article
C2 - 15357953
AN - SCOPUS:4444335344
SN - 1074-7613
VL - 21
SP - 429
EP - 441
JO - Immunity
JF - Immunity
IS - 3
ER -
