Abstract
Type 2 helper T cells (T(H)2) are critically involved in allergies and asthma. Here we demonstrate that extracellular matrix protein-1 (ECM1) is highly and selectively expressed in T(H)2 cells. ECM1 deficiency caused impaired T(H)2 responses and reduced allergic airway inflammation in vivo. Functional analysis demonstrated that although the T(H)2 polarization of ECM1-deficient cells was unimpaired, these cells had a defect in migration and were retained in peripheral lymphoid organs. This was associated with reduced expression of KLF2 and S1P(1). We also found that ECM1 could directly bind the interleukin-2 (IL-2) receptor to inhibit IL-2 signaling and activate S1P(1) expression. Our data identify a previously unknown function of ECM1 in regulating T(H)2 cell migration through control of KLF2 and S1P(1) expression.
MeSH terms
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Adoptive Transfer
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Animals
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Cell Differentiation / genetics
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Cell Differentiation / immunology
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Cell Movement / genetics
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Cell Movement / immunology
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Cells, Cultured
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Disease Models, Animal
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Extracellular Matrix Proteins / genetics
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Extracellular Matrix Proteins / immunology
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Extracellular Matrix Proteins / metabolism*
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Gene Expression Regulation / immunology
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Humans
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Hypersensitivity / immunology*
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Lymph Nodes / pathology
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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 / immunology
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Nerve Tissue Proteins / metabolism*
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Receptors, Lymphocyte Homing / genetics
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Receptors, Lymphocyte Homing / immunology
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Receptors, Lymphocyte Homing / metabolism*
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Signal Transduction / immunology
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Th2 Cells / immunology
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Th2 Cells / metabolism*
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Th2 Cells / pathology
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Transgenes / genetics
Substances
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Ecm1 protein, mouse
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Extracellular Matrix Proteins
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Nerve Tissue Proteins
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Receptors, Lymphocyte Homing
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Sip1 protein, mouse