CsCCL17, a CC chemokine of Cynoglossus semilaevis, induces leukocyte trafficking and promotes immune defense against viral infection.

CC chemokines are the largest subfamily of chemokines, which are important components of the innate immune system. To date, sequences of several CC chemokines have been identified in half-smooth tongue sole (Cynoglossus semilaevis); however, the activities and functions of these putative chemokines remain unknown. Herein, we characterized a CC chemokine, CsCCL17, from tongue sole, and examined its activity. CsCCL17 contains a 303 bp open reading frame, which encodes a polypeptide of 100 amino acids with a molecular mass of 12 kDa CsCCL17 is phylogenetically related to the CCL17/22 group of CC chemokines and possesses the typical arrangement of four cysteines and an SCCR motif found in known CC chemokines. Under normal physiological conditions, CsCCL17 expression was detected in spleen, liver, heart, gill, head kidney, muscle, brain, and intestine. When the fish were infected by bacterial and viral pathogens, CsCCL17 expression was significantly up-regulated in a time-dependent manner. Chemotactic analysis showed that recombinant CsCCL17 (rCsCCL17) induced migration of peripheral blood leukocytes. A mutagenesis study showed that when the two cysteine residues in the SCCR motif were replaced by serine, no apparent chemotactic activity was observed in the mutant protein rCsCCL17M. rCsCCL17 enhanced the resistance of tongue sole against viral infection, but rCsCCL17M lacked this antiviral effect. Taken together, these findings indicate that CsCCL17 is a functional CC chemokine with the ability to recruit leukocytes and enhance host immune defense in a manner that requires the conserved SCCR motif.