A neuronal receptor, neuropilin-1, is essential for the initiation of the primary immune response

The initiation of a primary immune response requires contact between dendritic cells (DCs) and resting T cells. However, little is known about the proteins that mediate this initial contact. We show here that neuropilin-1, a receptor involved in axon guidance, was expressed by human DCs and resting T cells both in vitro and in vivo. The initial contact between DCs and resting T cells led to neuropilin-1 polarization on T cells. DCs and resting T cells specifically bound soluble neuropilin-1, and resting T cells formed clusters with neuropilin-1–transfected COS-7 cells in a neuropilin-1–dependent manner. Functionally, preincubation of DCs or resting T cells with blocking neuropilin-1 antibodies inhibited DC-induced proliferation of resting T cells. These data suggest that neuropilin-1 mediates interactions between DCs and T cells that are essential for initiation of the primary immune response and show parallels between the nervous and immune systems.

[1]  Shay Soker,et al.  Neuropilin-1 Is Expressed by Endothelial and Tumor Cells as an Isoform-Specific Receptor for Vascular Endothelial Growth Factor , 1998, Cell.

[2]  M. Al-Alwan,et al.  Cutting Edge: The Dendritic Cell Cytoskeleton Is Critical for the Formation of the Immunological Synapse1 , 2001, The Journal of Immunology.

[3]  M. Poo,et al.  Conversion of neuronal growth cone responses from repulsion to attraction by cyclic nucleotides. , 1998, Science.

[4]  M. Schachner,et al.  Analysis of the L1-Deficient Mouse Phenotype Reveals Cross-Talk between Sema3A and L1 Signaling Pathways in Axonal Guidance , 2000, Neuron.

[5]  A. Kolodkin Semaphorin-mediated neuronal growth cone guidance. , 1998, Progress in brain research.

[6]  C. Goodman,et al.  Neuropilin-2, a Novel Member of the Neuropilin Family, Is a High Affinity Receptor for the Semaphorins Sema E and Sema IV but Not Sema III , 1997, Neuron.

[7]  S. Strittmatter,et al.  PlexinA1 Autoinhibition by the Plexin Sema Domain , 2001, Neuron.

[8]  H Stein,et al.  Immunoenzymatic labeling of monoclonal antibodies using immune complexes of alkaline phosphatase and monoclonal anti-alkaline phosphatase (APAAP complexes). , 1984, The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society.

[9]  Alex L Kolodkin,et al.  Neuropilin Is a Semaphorin III Receptor , 1997, Cell.

[10]  R. Zaru,et al.  Exclusion of CD45 from the T-cell receptor signaling area in antigen-stimulated T lymphocytes , 2000, Current Biology.

[11]  A. Kolodkin,et al.  Semaphorin Signaling A Little Less Per-Plexin , 1999, Neuron.

[12]  P. Gaulard,et al.  Erythroblasts are a source of angiogenic factors. , 2001, Blood.

[13]  M. Poo,et al.  Unified Nomenclature for the Semaphorins/Collapsins , 1999, Cell.

[14]  L. Boumsell,et al.  Immunohistochemical detection of cd1a antigen in formalin‐fixed and paraffin‐embedded tissue sections with monoclonal antibody 010 , 1993, The Journal of pathology.

[15]  M. Soloski,et al.  Physiological Regulation of the Immunological Synapse by Agrin , 2001, Science.

[16]  C. Goodman,et al.  The semaphorin genes encode a family of transmembrane and secreted growth cone guidance molecules , 1993, Cell.

[17]  Michael L. Dustin,et al.  The immunological synapse and the actin cytoskeleton: molecular hardware for T cell signaling , 2000, Nature Immunology.

[18]  S. Soker,et al.  Identification of a natural soluble neuropilin-1 that binds vascular endothelial growth factor: In vivo expression and antitumor activity. , 2000, Proceedings of the National Academy of Sciences of the United States of America.

[19]  R. Steinman,et al.  Dendritic cells and the control of immunity , 1998, Nature.

[20]  F. Geissmann,et al.  Transforming Growth Factor (cid:98) 1, in the Presence of Granulocyte/Macrophage Colony-stimulating Factor and Interleukin 4, Induces Differentiation of Human Peripheral Blood Monocytes into Dendritic Langerhans Cells , 2022 .

[21]  H. Drexhage,et al.  Homotypic cluster formation of dendritic cells, a close correlate of their state of maturation. Defects in the biobreeding diabetes‐prone rat , 2001, Journal of leukocyte biology.

[22]  Boris Barbour,et al.  Functional antigen-independent synapses formed between T cells and dendritic cells , 2001, Nature Immunology.

[23]  P. Romeo,et al.  Neuropilin-1 is expressed on bone marrow stromal cells: a novel interaction with hematopoietic cells? , 1999, Blood.

[24]  Y. Rao,et al.  The neuronal repellent Slit inhibits leukocyte chemotaxis induced by chemotactic factors , 2001, Nature.

[25]  C. Figdor,et al.  Identification of DC-SIGN, a Novel Dendritic Cell–Specific ICAM-3 Receptor that Supports Primary Immune Responses , 2000, Cell.

[26]  M. Tessier-Lavigne,et al.  Neuropilin Is a Receptor for the Axonal Chemorepellent Semaphorin III , 1997, Cell.

[27]  Zhigang He,et al.  Semaphorin–Neuropilin Interactions Underlying Sympathetic Axon Responses to Class III Semaphorins , 1998, Neuron.