ECM1 controls Th2 cell egress from lymph nodes through re-expression of S1P1 (102.3)

Abstract

Abstract The T helper 2 (Th2) subset of T cell is critically involved in allergy and asthma. In this study, we demonstrate that the Extra-Cellular Matrix protein 1 (ECM1), a secreted protein, 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 Th2 polarization was unimpaired, ECM1 deficient Th2 (but not Th1) cells exhibited a defect in migration and were retained in peripheral lymphoid organs. This was associated with reduced expression of the transcription factor klf2 and its downstream target, the chemokine receptor S1P1 and could be corrected by retroviral transduction of individual members of the pathway. We also found that ECM1 can directly bind to IL-2 receptor to inhibit IL-2 signaling and activate S1P1 expression. Our data identify a novel function of ECM1 in regulating Th2 cell migration through controlling of klf2 and S1P1 expression.