IL-2 Signaling Couples the MAPK and mTORC1 Axes to Promote T Cell Proliferation and Differentiation in Teleosts

被引:30
作者
Mu, Pengfei [1 ,2 ]
Huo, Jieying [1 ,2 ]
Li, Xiaofeng [1 ]
Li, Wanru [1 ]
Li, Xiaomeng [1 ]
Ao, Jingqun [2 ,5 ]
Chen, Xinhua [1 ,2 ,3 ,4 ]
机构
[1] Fujian Agr & Forestry Univ, Inst Oceanol, Key Lab Marine Biotechnol Fujian Prov, Fuzhou, Peoples R China
[2] Minist Nat Resources, Inst Oceanog 3, Key Lab Marine Biogenet Resources, Xiamen, Peoples R China
[3] Qingdao Natl Lab Marine Sci & Technol, Lab Marine Biol & Biotechnol, Qingdao, Peoples R China
[4] Fujian Agr & Forestry Univ, 15 Shangxiadian Rd, Fuzhou 350002, Peoples R China
[5] Minist Nat Resources, Inst Oceanog 3, 184 Daxue Rd, Xiamen 361005, Peoples R China
基金
中国国家自然科学基金; 国家重点研发计划;
关键词
ADAPTIVE IMMUNITY; INTERLEUKIN-2; RECEPTOR; EVOLUTION; CHAIN; EXPRESSION; GAMMA; FISH; POPULATIONS; BIOACTIVITY;
D O I
10.4049/jimmunol.2100764
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
IL-2 is a pleiotropic cytokine that is critical for T cell immunity. Although the IL-2 -mediated regulation of T cell immunity in mammals is relatively well understood, it remains largely unknown whether and how IL-2 regulates T cell immunity in lower vertebrates. To address this knowledge gap, we investigated the role played by IL-2 in the regulation of T cell response, as well as the associated underlying mechanisms in a teleost fish, large yellow croaker (Larimichthys crocea). We found that large yellow croaker (L. crocea) IL-2 (LcIL-2) significantly promoted T cell proliferation both in vivo and in vitro; significantly induced the differentiation of Th1, Th2, regulatory T, and cytotoxic T cells while inhibiting Th17 differentiation; and participated in the elimination of invading pathogenic bacteria. Mechanistically, the binding of LcIL-2 to its heterotrimer receptor complex (LcIL-15Ra/LcIL-2Rb/Lcgc) triggered the conserved JAK-STAT5 pathway, which in turn regulated the expression of genes involved in T cell expansion, differentiation, and biological function. The MAPK and mammalian target of rapamycin complex 1 (mTORC1) axes, which are involved in TCR-mediated signaling, were also required for LcIL-2-mediated T cell response. Collectively, our results demonstrated that fish IL-2 plays a comprehensive regulatory role in T cell response and highlighted the complex and delicate network regulating T cell -driven immune response. We propose that T cell immunity is regulated by the interplay between TCR signaling and cytokine signaling, and that this basic strategy evolved before the emergence of the tetrapod lineage. Our findings provide valuable insights into the regulatory mechanisms underlying T cell response in teleosts. The Journal of 208: 1616-1631.
引用
收藏
页码:1616 / 1631
页数:17
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