Li Qiuhua, Chen Yuhong, Wang Meiyan, Li Chenhao, Ao Jingqun, Chen Xinhua
State Key Laboratory of Mariculture Breeding, Key Laboratory of Marine Biotechnology of Fujian Province, College of Marine Sciences, Fujian Agriculture and Forestry University, Fuzhou, 350002, China; Guangdong Provincial Key Laboratory of Marine Biology, Shantou University, Shantou, 515063, China.
State Key Laboratory of Mariculture Breeding, Key Laboratory of Marine Biotechnology of Fujian Province, College of Marine Sciences, Fujian Agriculture and Forestry University, Fuzhou, 350002, China; Fujian Provincial Fisheries Technology Extension Center, Fuzhou, China.
Fish Shellfish Immunol. 2025 Oct;165:110550. doi: 10.1016/j.fsi.2025.110550. Epub 2025 Jul 9.
The B7 family provides critical co-stimulatory signals for T cell activation through receptor interactions, thereby modulating T cell proliferation and function. However, the roles and downstream signaling pathways of these molecules in teleosts remain largely unexplored. In the present study, we identified a B7-H3 homologue (LcB7-H3) in large yellow croaker (Larimichthys crocea), a commercially significant marine teleost species. The deduced LcB7-H3 protein contains conserved extracellular IgV-like and IgC-like domains, and phylogenetic analysis revealed its clustering with vertebrate B7-H3 homologues. It is constitutively expressed in all examined tissues and immune cells, with particularly high expression levels in mucosal tissues and primary head kidney monocytes/macrophages (PKMs). The recombinant LcB7-H3 protein (rLcB7-H3) significantly enhanced T cell proliferation and upregulated interleukin-2 expression, which is a hallmark of teleost T cell activation. Furthermore, rLcB7-H3 increased phosphorylation levels of MEK1/2 and ERK1/2 in the MAPK/ERK signaling pathway, as well as mTOR and 4E-BP1 in the mTOR signaling pathway. Collectively, these findings demonstrate that LcB7-H3 may promote T cell proliferation and activation via MAPK/ERK and mTOR pathways, suggesting evolutionarily conserved roles among vertebrate B7-H3 homologues.
B7家族通过受体相互作用为T细胞活化提供关键的共刺激信号，从而调节T细胞增殖和功能。然而，这些分子在硬骨鱼中的作用和下游信号通路在很大程度上仍未被探索。在本研究中，我们在大黄鱼（Larimichthys crocea）中鉴定出一种B7-H3同源物（LcB7-H3），大黄鱼是一种具有重要商业价值的海洋硬骨鱼物种。推导的LcB7-H3蛋白包含保守的细胞外IgV样和IgC样结构域，系统发育分析显示它与脊椎动物B7-H3同源物聚类。它在所有检测的组织和免疫细胞中组成性表达，在黏膜组织和原代头肾单核细胞/巨噬细胞（PKM）中表达水平特别高。重组LcB7-H3蛋白（rLcB7-H3）显著增强T细胞增殖并上调白细胞介素-2的表达，白细胞介素-2是硬骨鱼T细胞活化的一个标志。此外，rLcB7-H3增加了MAPK/ERK信号通路中MEK1/2和ERK1/2的磷酸化水平，以及mTOR信号通路中mTOR和4E-BP1的磷酸化水平。总的来说，这些发现表明LcB7-H3可能通过MAPK/ERK和mTOR途径促进T细胞增殖和活化，提示脊椎动物B7-H3同源物之间存在进化上保守的作用。
