%A Ravindra Gujar
%A Pradip Sen
%O Copyright of this article belongs to Elsevier Science.
%J Cytokine
%T Transforming growth factor-?1 impairs lymph node homing of dendritic cells by downregulating C-type lectin receptor-2 expression.
%X 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)-?1, however, inhibits migration of DCs by downregulating the expression of chemokine receptor CCR-7. Whether TGF-?1 engages any other receptor to mediate this inhibitory effect is currently unknown. In this article, we report that TGF-?1 attenuated the lymph node homing ability of mouse DCs by reducing C-type lectin receptor-2 (CLEC-2) expression. Notably, TGF-?1 inhibited CLEC-2 expression in DCs via c-Src. DCs silenced for c-Src were resistant to TGF-?1-induced inhibition of CLEC-2 expression. Furthermore, silencing of c-Src substantially improved the lymph node homing capacity of TGF-?1-treated DCs by restoring CLEC-2 expression. These results document a critical role for c-Src and CLEC-2 in TGF-?1-mediated impairment of DC migration and define a previously unknown mechanism by which TGF-?1 attenuates the lymph node homing ability of DCs.
%K C-type lectin receptor; Dendritic cell trafficking; Immunosuppressive cytokines; c-Src
%P 39-43
%V 110
%D 2018
%I Elsevier Science Ltd
%L open2089