Interleukin (IL)-10 is an important regulatory cytokine that regulates both, innate and adaptive immunity. Mammalian IL-10 is produced by many cell types but primarily by antigen-specific T-lymphocytes and macrophages, and regulates the proliferation and differentiation of B- and T-lymphocytes after antigen recognition. IL-10 inhibits the production of reactive oxygen and nitrogen radicals in activated macrophages, and can redirect the immune response from a type-I (pro-inflammatory) to a type II (anti-inflammatory) immune response by suppressing the production of pro-inflammatory cytokines. homologue of mammalian IL-10 has been identified in several fish species but very few studies have reported on its functional characterization. In the present study, we report on the production of recombinant carp IL-10 and its biological activities on carp leukocytes in vitro. Similar to mammalian IL-10, recombinant carp IL-10 shows to be a potent inhibitor of the respiratory burst induced by PMA and of nitric oxide production induced by LPS. IL-10 also downregulates the expression of pro-inflammatory cytokines such as interleukin-1beta. Upon binding to its receptor, IL-10 signals via the JAK/STAT pathway. The activation of JAK1 results in the phosphorylation of the cytosolic tails of the IL-10 receptor-1 (IL-10R1) which in turns facilitates the recruitment and phosphorylation of STAT3. Phospho-STAT3 induces the expression of SOCS3 leading to the downregulation of pro-inflammatory cytokines. A carp genome-based analysis shows the presence of duplicated genes for the IL-10R1, both possessing one conserved JAK1 docking site and two and maybe three STAT3 phosphorylation sites. Both genes are equally expressed in several carp tissues and cell types. Western blot analysis of head kidney leukocytes stimulated with recombinant carp IL-10, revealed increased levels of phospho-STAT3 within minutes after stimulation. We also observed an upregulation of SOCS3 gene expression in carp kidney leukocytes upon stimulation with recombinant IL-10. Altogether, our results suggest a conservation of the signaling pathway as well as anti-inflammatory activities of carp IL-10.
Piazzon de Haro, M. C., Forlenza, M., & Wiegertjes, G. F. (2013). Anti-inflammatory and modulatory activities of carp IL-10. Fish and Shellfish Immunology, 34(6), 1672-1673. https://doi.org/10.1016/j.fsi.2013.03.120