Interleukin (IL)-10, an immune-regulatory cytokine, exerts various biological functions through interaction with IL-10 receptors. In teleost, very limited functional studies on IL-10 receptors have been documented. In this study, we reported the expression patterns of IL-10 receptor 1 (CsIL-10R1) and receptor 2 (CsIL-10R2) of tongue sole (Cynoglossus semilaevis) and examined their biological properties. The expression of CsIL-10R1 and CsIL-10R2 occurred in multiple tissues and were regulated by bacterial challenge. In vitro binding studies showed that recombinant extracellular region of CsIL-10R1 (rCsIL-10R1ex) rather than rCsIL-10R2ex could bind with rCsIL-10. Cellular study showed that both CsIL-10R1 and CsIL-10R2 were expressed on peripheral blood leukocytes (PBLs), and blockade of CsIL-10R1 or CsIL-10R2 by antibody could reduce inhibitory effect of CsIL-10 on ROS production of PBLs. When injected in vivo, anti-rCsIL-10R1 or anti-rCsIL-10R2 antibody dramatically promoted the expression of proinflammatory cytokines and suppressed bacterial dissemination in tongue sole tissues. Consistently, the overexpression of CsIL-10R1 or CsIL-10R2 significantly enhanced bacterial dissemination, and the overexpression of CsIL-10R1M bearing STAT3 site mutation reduced bacterial dissemination. Overall, these results demonstrate for the first time teleost IL-10 receptors play a negative role in antibacterial immunity and add insight into the function of CsIL-10 receptors.

白细胞介素 (IL)-10 是一种免疫调节细胞因子，通过与 IL-10 受体相互作用发挥各种生物学功能。在硬骨鱼中，对 IL-10 受体的功能研究非常有限。在本研究中，我们报道了舌鳎（Cynoglossus semilaevis）的 IL-10 受体 1 (CsIL-10R1) 和受体 2 (CsIL-10R2) 的表达模式，并检查了它们的生物学特性。CsIL-10R1 和 CsIL-10R2 的表达发生在多个组织中，并受细菌攻击的调节。体外结合研究表明，CsIL-10R1 (rCsIL-10R1ex) 的重组胞外区而非 rCsIL-10R2ex 可以与 rCsIL-10 结合。细胞研究表明，CsIL-10R1和CsIL-10R2均在外周血白细胞（PBLs）上表达，抗体阻断CsIL-10R1或CsIL-10R2可降低CsIL-10对PBLs产生ROS产生的抑制作用。体内注射时，抗rCsIL-10R1或抗rCsIL-10R2抗体显着促进促炎细胞因子的表达并抑制舌底组织中的细菌传播。一致地，CsIL-10R1 或 CsIL-10R2 的过表达显着增强了细菌传播，而带有 STAT3 位点突变的 CsIL-10R1M 的过表达减少了细菌传播。总体而言，这些结果首次证明硬骨鱼 IL-10 受体在抗菌免疫中起负面作用，并增加了对 CsIL-10 受体功能的了解。