ECM1 controls TH2 cell egress from lymph nodes through re-expression of S1P1
Z Li, Y Zhang, Z Liu, X Wu, Y Zheng, Z Tao, K Mao… - Nature …, 2011 - nature.com
Nature immunology, 2011•nature.com
Type 2 helper T cells (TH2) are critically involved in allergies and asthma. Here we
demonstrate that extracellular matrix protein-1 (ECM1) is highly and selectively expressed in
TH2 cells. ECM1 deficiency caused impaired TH2 responses and reduced allergic airway
inflammation in vivo. Functional analysis demonstrated that although the TH2 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 …
demonstrate that extracellular matrix protein-1 (ECM1) is highly and selectively expressed in
TH2 cells. ECM1 deficiency caused impaired TH2 responses and reduced allergic airway
inflammation in vivo. Functional analysis demonstrated that although the TH2 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 …
Abstract
Type 2 helper T cells (TH2) are critically involved in allergies and asthma. Here we demonstrate that extracellular matrix protein-1 (ECM1) is highly and selectively expressed in TH2 cells. ECM1 deficiency caused impaired TH2 responses and reduced allergic airway inflammation in vivo. Functional analysis demonstrated that although the TH2 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 S1P1. We also found that ECM1 could directly bind the interleukin-2 (IL-2) receptor to inhibit IL-2 signaling and activate S1P1 expression. Our data identify a previously unknown function of ECM1 in regulating TH2 cell migration through control of KLF2 and S1P1 expression.
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