Transforming growth factor-β1 impairs lymph node homing of dendritic cells by downregulating C-type lectin receptor-2 expression. (October 2018)

• Record Type: Journal Article
• Authors: Gujar, Ravindra; Sen, Pradip
• Is Part Of: Cytokine. Volume 110(2018)
• Page Start: 39
• Page End: 43
• Publication Date: 2018-10
• Subjects: c-Src -- C-type lectin receptor -- Dendritic cell trafficking -- Immunosuppressive cytokines; BMDC bone marrow-derived dendritic cell -- Btk Bruton's tyrosine kinase -- CLEC-2 C-type lectin receptor-2 -- DC dendritic cell -- GM-CSF granulocyte-macrophage colony-stimulating factor -- HGF hepatocyte growth factor -- IL interleukin -- LFA1 lymphocyte function-associated antigen 1 -- LPS lipopolysaccharide -- MZ marginal zone -- PDPN podoplanin -- PE phycoerythrin -- SFK Src family kinase -- siRNA small interfering RNA -- TGF transforming growth factor -- Tyr tyrosine; Cytokines -- Periodicals; 571.844
• DOI: 10.1016/j.cyto.2018.04.023
• Languages: English
• ISSNs: 1043-4666

Abstract

Highlights: TGF-β1 impedes DC migration to regional lymph nodes by reducing CLEC-2 expression. TGF-β1 downregulates CLEC-2 expression in DCs via c-Src. c-Src silencing improves lymph node homing of TGF-β1-treated DCs restoring CLEC-2 level. Abstract: 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)-β1, however, inhibits migration of DCs by downregulating the expression of chemokine receptor CCR-7. Whether TGF-β1 engages any other receptor to mediate this inhibitory effect is currently unknown. In this article, we report that TGF-β1 attenuated the lymph node homing ability of mouse DCs by reducing C-type lectin receptor-2 (CLEC-2) expression. Notably, TGF-β1 inhibited CLEC-2 expression in DCs via c-Src. DCs silenced for c-Src were resistant to TGF-β1-induced inhibition of CLEC-2 expression. Furthermore, silencing of c-Src substantially improved the lymph node homing capacity of TGF-β1-treated DCs by restoring CLEC-2 expression. These results document a critical role for c-Src and CLEC-2 in TGF-β1-mediated impairment of DC migration and define a previously unknown mechanism by which TGF-β1 attenuates the lymph node homing ability of DCs.