LAUSR

HighlightsTGF‐&bgr;1 impedes DC migration to regional lymph nodes by reducing CLEC‐2 expression.TGF‐&bgr;1 downregulates CLEC‐2 expression in DCs via c‐Src.c‐Src silencing improves lymph node homing of TGF‐&bgr;1‐treated DCs restoring CLEC‐2 level. &NA; Trafficking of dendritic cells (DCs) from peripheral tissues to draining lymph nodes is a prerequisite for induction of adaptive immunity. An immunosuppressive cytokine transforming growth factor (TGF)‐&bgr;1, however, inhibits migration of DCs by downregulating the expression of chemokine receptor CCR‐7. Whether TGF‐&bgr;1 engages any other receptor to mediate this inhibitory effect is currently unknown. In this article, we report that TGF‐&bgr;1 attenuated the lymph node homing ability of mouse DCs by reducing C‐type lectin receptor‐2 (CLEC‐2) expression. Notably, TGF‐&bgr;1 inhibited CLEC‐2 expression in DCs via c‐Src. DCs silenced for c‐Src were resistant to TGF‐&bgr;1‐induced inhibition of CLEC‐2 expression. Furthermore, silencing of c‐Src substantially improved the lymph node homing capacity of TGF‐&bgr;1‐treated DCs by restoring CLEC‐2 expression. These results document a critical role for c‐Src and CLEC‐2 in TGF‐&bgr;1‐mediated impairment of DC migration and define a previously unknown mechanism by which TGF‐&bgr;1 attenuates the lymph node homing ability of DCs.