Abstract
Precise intrathymic cell migration is important for thymocyte maturation and organ architecture. The orchestration of thymocyte trafficking, however, is not well understood at a molecular level. Here, we described highly regulated plexinD1 expression on CD4+CD8+ double positive (DP) thymocytes. PlexinD1 expression was further affected by the engagement of T cell receptor complex. Activation of plexinD1 via the ligand, semaphorin 3E, repressed CCL25 chemokine signaling via its receptor CCR9 in CD69+ thymocytes. In the absence of plexinD1, CD69+ thymocytes remained in the cortex, maturing to form ectopic single positive (SP) thymocyte clusters in Plxnd1-deficient fetal liver cell-transplanted mice. As a consequence, the boundary between DP and SP thymocytes at corticomedullary junctions was disrupted and medullary structures formed under the thymic capsule. These results demonstrate the importance of plexinD1 in directing migration of maturing thymocytes via modulation of biological responses to chemokine gradients.
Publication types
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Research Support, N.I.H., Extramural
MeSH terms
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Animals
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Antigens, CD / immunology
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Antigens, Differentiation, T-Lymphocyte / immunology
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Cell Movement / genetics
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Cell Movement / immunology*
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Cytoskeletal Proteins
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Gene Expression Profiling
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Glycoproteins / genetics
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Glycoproteins / metabolism*
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Intracellular Signaling Peptides and Proteins
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Lectins, C-Type
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Membrane Glycoproteins / genetics
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Membrane Glycoproteins / metabolism*
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Membrane Proteins / genetics
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Membrane Proteins / metabolism*
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Mice
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Mice, Knockout
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Nerve Tissue Proteins / genetics
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Nerve Tissue Proteins / metabolism*
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Receptors, CCR / metabolism
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Semaphorins
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T-Lymphocyte Subsets / cytology
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T-Lymphocyte Subsets / immunology*
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T-Lymphocyte Subsets / metabolism
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Thymus Gland / cytology
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Thymus Gland / immunology*
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Thymus Gland / metabolism
Substances
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Antigens, CD
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Antigens, Differentiation, T-Lymphocyte
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CC chemokine receptor 9
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CD69 antigen
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Cytoskeletal Proteins
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Glycoproteins
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Intracellular Signaling Peptides and Proteins
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Lectins, C-Type
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Membrane Glycoproteins
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Membrane Proteins
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Nerve Tissue Proteins
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Plxnd1 protein, mouse
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Receptors, CCR
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Sema3e protein, mouse
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Semaphorins