ECM1 controls T(H)2 cell egress from lymph nodes through re-expression of S1P(1).
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:
Adoptive Transfer, Animals, Cell Differentiation, Cell Movement, Cells, Cultured, Disease Models, Animal, Extracellular Matrix Proteins, Gene Expression Regulation, Humans, Hypersensitivity, Lymph Nodes, Mice, Mice, Knockout, Nerve Tissue Proteins, Receptors, Lymphocyte Homing, Signal Transduction, Th2 Cells, Transgenes
Adoptive Transfer, Animals, Cell Differentiation, Cell Movement, Cells, Cultured, Disease Models, Animal, Extracellular Matrix Proteins, Gene Expression Regulation, Humans, Hypersensitivity, Lymph Nodes, Mice, Mice, Knockout, Nerve Tissue Proteins, Receptors, Lymphocyte Homing, Signal Transduction, Th2 Cells, Transgenes
Nat. Immunol.
Date: Feb. 01, 2011
PubMed ID: 21217760
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