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Leukocyte cell-derived chemotaxin 2 (LECT2) is a multifunctional protein of the innate immune system that defends against bacterial infections and chemotactic activity. However, its precise function in lamprey remains unclear. In this study, a novel LECT2 gene was first cloned from Lampetra japonica. The full-length cDNA sequence of L-LECT2 consists of a 606-bp ORF encoding a protein of 201 amino acid residues. L-LECT2 has greater than 50% sequence identity with its homologs in jawed vertebrates. FACS and immunohistochemistry assays were used to determine that the L-LECT2 protein was primarily distributed in the intestines and supraneural body tissues of lamprey, also marginally detectable in leukocytes. However, the expression of L-LECT2 was differentially upregulated in the intestines and heart after treatment with LPS. The recombinant L-LECT2 resulted in significant promoting migration of the leukocytes in vitro. Our data demonstrate that L-LECT2 treatment could enhance phagocytosis in lamprey large lymphocytes. Thus, our results suggest that LECT2 can modulate the host defense in lamprey and mediate antibacterial protection against E.coli through large lymphocytes.A novel LECT2 gene was cloned from Lampetra japonica.The expression of L-LECT2 was differentially upregulated in the intestines and heart after treatment with LPS.L-LECT2 treatment resulted in significant promoting migration of the leukocytes in vitro.L-LECT2 treatment could enhance phagocytosis and bacterial killing in lamprey large lymphocytes.