Identification of duck IL-4 and its inhibitory effect on IL-17A expression in R. anatipestifer-stimulated splenic lymphocytes

Authors: FERNANDEZ, CHERRY - Gyeongsang National University; AFRIN, FAHMIDA - Gyeongsang National University; FLORES, ROCHELLE - Gyeongsang National University; KIM, WOO - Gyeongsang National University; JEONG, JIPSEOL - Gyeongsang National University; KIM, WOOHYUN - Gyeongsang National University; Lillehoj, Hyun; MIN, WONGI - Gyeongsang National University

Submitted to: Molecular Immunology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 3/1/2018
Publication Date: 6/1/2018
Citation: Fernandez, C.P., Afrin, F., Flores, R.A., Kim, W.H., Jeong, J., Kim, W., Lillehoj, H.S., Min, W. 2018. Identification of duck IL-4 and its inhibitory effect on IL-17A expression in R. anatipestifer-stimulated splenic lymphocytes. Molecular Immunology. 95:20-29. https://doi.org/10.1016/j.molimm.2018.01.009.
DOI: https://doi.org/10.1016/j.molimm.2018.01.009

Interpretive Summary: Limited understanding about how immune system works in bird species hinders progress in developing disease prevention strategies in bird species including duck and poultry. Interleukin (IL-4) is produced by a wide range of immune cells and plays an important effector function in disease process. In this paper, university scientists in South Korea collaborated with ARS scientists to identify a cytokine called IL-4 with diverse biological functions; it not only promotes immune response and homeostasis but is also involved in immune regulation. Using an infection caused by R. anatipestifer, a gram-negative extracellular bacterium which is the most economically important major infectious pathogen affecting the duck industry, these scientists identified IL-4 and showed that infection with R. anatipestifer serotype 7 generally inhibited the expression of IL-4. Collectively, these results provide the new information on IL-4 in duck species and offer strong evidence of its anti-inflammatory effects on R. anatipestifer-stimulated lymphocytes. Further studies are necessary to determine its role in disease process.

Technical Abstract: As the dysregulation of IL-17 is implicated in the pathogenesis of various autoimmune and inflammatory diseases, the suppression of IL-17 production by Th2 cytokines could alleviate the development of these diseases. Previously, we confirmed that inflammatory cytokines including IL-17A are strongly associated with R. anatipestifer infection, which is one of the most important bacterial pathogens in the duck industry. Here, we found that IL-4 treatment downregulated the expression of IL-17A and IL-17F transcripts in splenic lymphocytes stimulated with R. anatipestifer. Moreover, duck IL-4 (duIL-4) treatment in R. anatipestifer-stimulated lymphocytes suppressed the expression of IL-23p19 and IL-12p40 transcripts compared to untreated and stimulated lymphocytes. Conversely, duIL-4 increased levels of IFN-' and IL-10. We identified a full-length duIL-4 cDNA encoding 136 amino acids from ConA-activated splenic lymphocytes that shares 49.3 -50% amino acid sequence identity with chicken and quail IL-4 and 21 -29.7% with mammalian and piscine homologues. Low or moderate levels of duIL-4 transcript were observed in healthy tissues, including the spleen, bursa, and thymus, whereas duIL-4 expression was higher in the kidney and lung. Levels of duIL-4 were generally upregulated in mitogen-activated splenic lymphocytes but lower in the liver and spleen of R. anatipestifer-infected ducks compared to those of infected chickens. Recombinant duIL-4 promoted nitric oxide synthesis in duck macrophages stimulated by R. anatipestifer compared to untreated and stimulated control macrophages. These results demonstrate that IL-4 is an important Th2 cytokine that inhibits inflammatory responses in splenic lymphocytes stimulated with R. anatipestifer.