草鱼IL-20通过IL-20R1诱导STAT3磷酸化的免疫信号机制研究

Abstract

IL-20 is a pleiotropic cytokine that belongs to the IL-10 family and has a variety of biological functions in tissue homeostasis and regulation of host immune defenses. It signals through a heterodimeric receptor composed of a subunit with a long intracellular domain (R1 type receptor) and a subunit with a short intracellular domain (R2 type receptor). In this study, the R1 type receptor ( Ci IL-20R1/CRFB8) and the R2 type receptor ( Ci IL-20R2/CRFB16) were identified in grass carp Ctenopharyngodon idella. Expression analysis revealed that IL-20R2 was highly expressed in the gills and skin in healthy fish. Infection with Flavobacterium columnare resulted in the downregulation of both receptors in the gill at 48 and 72 h, whilst infection with grass carp reovirus induced their expression in the head kidney and spleen at 72 h. In the primary head kidney leucocytes, the expression levels of IL-20R1 and IL-20R2 were decreased after stimulation with 250 ng/mL IL-1β but not affected by IFN-γ. Co-immunoprecipitation analysis showed that Ci IL-20R2/CRFB16 but not Ci IL-20R1/CRFB8 bound to Ci IL-20L. Furthermore, it was shown that Ci IL-20R1/CRFB8 was responsible for activating the phosphorylation of STAT3 , whilst Ci IL-20R2/CRFB16 was not involved. Structural modeling analysis showed that key residues involved in the interaction between IL-20 and receptors were highly conserved between grass carp and humans, suggesting that the signal transduction and functions of IL-20/IL-20R axis are evolutionarily conserved.