D-dopachrome tautomerase from Japanese sea bass(Lateolabrax japonicus) is a chemokine-like cytokine and functional homolog of macrophage migration inhibitory factor

作     者：Feng Xu Ming-Yun Li Jiong Chen Feng Xu;Ming-Yun Li;Jiong Chen

作者机构：State Key Laboratory for Managing Biotic and Chemical Threats to the Quality and Safety of Agro-ProductsNingbo UniversityNingboZhejiang 315211China Laboratory of Biochemistry and Molecular BiologySchool of Marine SciencesNingbo UniversityNingboZhejiang 315832China Key Laboratory of Applied Marine Biotechnology of Ministry of EducationNingbo UniversityNingboZhejiang 315832China 

出 版 物：《Zoological Research》 (动物学研究（英文）)

年 卷 期：2020年第41卷第1期

页      面：39-50页

核心收录：

学科分类：0710[理学-生物学] 07[理学] 071009[理学-细胞生物学] 

基　　金：supported by the National Natural Science Foundation of China(31772876) Zhejiang Provincial Natural Science Foundation of China(LZ18C190001) Scientific Innovation Team Project of Ningbo(2015C110018) K.C.Wong Magna Fund in Ningbo University 

主　　题：Cell migration D-dopachrome tautomerase Japanese sea bass Macrophage migration inhibitory factor Monocyte/macrophage 

摘      要：D-dopachrome tautomerase(DDT),a member of the macrophage migration inhibitory factor(MIF)protein superfamily,is a newly described cytokine with chemokine-like characteristics.However,research on fish DDT remains limited.In this study,we identified a DDT homolog(LjDDT)from the Japanese sea bass,Lateolabrax japonicus.Sequence analysis showed that LjDDT had typical sequence features of known DDT and MIF homologs and was most closely related to DDT of rock bream(Oplegnathus fasciatus).LjDDT transcripts were detected in all tested tissues of healthy Japanese sea bass,with the highest expression found in the liver.Upon infection with Vibrio harveyi,LjDDT transcripts were significantly down-regulated in the three tested tissues,including the liver,spleen,and head kidney.Recombinant LjDDT(rLjDDT)and the corresponding antibody(anti-rLjDDT)were subsequently prepared.The administration of 100μg/g anti-rLjDDT had a statistically significant protective effect on the survival of V.harveyi-infected fish.Moreover,rLjDDT was able to induce the migration of monocytes/macrophages(MO/MФ)and lymphocytes both in vitro and in vivo,but without significant influence on the migration of neutrophils.rLjDDT exhibited chemotactic activity for lipopolysaccharide(LPS)-stimulated M1-type MO/MΦin vitro,but not for cAMP-stimulated M2-type MO/MΦ.Furthermore,the knockdown of LjCD74,but not LjCXCR4,significantly down-regulated the rLjDDT-enhanced migration of MO/MΦand relieved the rLjMIF-inhibited migration of MO/MΦ.These results indicate that LjCD74 may be the major chemotactic receptor of LjDDT and LjMIF in Japanese sea bass MO/MΦ.Combined rLjDDT+rLjMIF treatment had no significant effect on the migration of MsiRNA,LjCD74si-,or LjCXCR4sitreated MO/MΦcompared to the control group,suggesting that the roles of LjDDT and LjMIF may be antagonistic.In conclusion,our study demonstrates for the first time that DDT may play a role in the immune responses of fish against bacterial infection through chemotactic recruitment of MO/MΦvia mediation of CD74 as an antagonist of MIF.