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Int. J. Mol. Sci. 2018, 19(6), 1665; https://doi.org/10.3390/ijms19061665

Interleukin-34 Regulates Th1 and Th17 Cytokine Production by Activating Multiple Signaling Pathways through CSF-1R in Chicken Cell Lines

1
Department of Animal Science and Technology, Chung-Ang University, Anseong 17546, Korea
2
Department of Biochemistry and Immunology, National Institute of Veterinary Research, 86 Truong Chinh, Dong Da, Hanoi 100000, Vietnam
3
Animal Biosciences and Biotechnology Laboratory, Agricultural Research Services, United States Department of Agriculture, Beltsville, MD 20705, USA
*
Author to whom correspondence should be addressed.
Received: 16 April 2018 / Revised: 19 May 2018 / Accepted: 2 June 2018 / Published: 5 June 2018
(This article belongs to the Special Issue Signaling Pathway of Immune Cells and Immune Disorder)
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Abstract

Interleukin-34 (IL-34) is a newly recognized cytokine with functions similar to macrophage colony-stimulating factor 1. It is expressed in macrophages and fibroblasts, where it induces cytokine production; however, the mechanism of chicken IL-34 (chIL-34) signaling has not been identified to date. The aim of this study was to analyze the signal transduction pathways and specific biological functions associated with chIL-34 in chicken macrophage (HD11) and fibroblast (OU2) cell lines. We found that IL-34 is a functional ligand for the colony-stimulating factor receptor (CSF-1R) in chicken cell lines. Treatment with chIL-34 increased the expression of Th1 and Th17 cytokines through phosphorylation of tyrosine and serine residues in Janus kinase (JAK) 2, tyrosine kinase 2 (TYK2), signal transducer and activator of transcription (STAT) 1, STAT3, and Src homology 2-containing tyrosine phosphatase 2 (SHP-2), which also led to phosphorylation of NF-κB1, p-mitogen-activated protein kinase kinase kinase 7 (TAK1), MyD88, suppressor of cytokine signaling 1 (SOCS1), and extracellular signal-regulated kinase 1 and 2 (ERK1/2). Taken together, these results suggest that chIL-34 functions by binding to CSF-1R and activating the JAK/STAT, nuclear factor κ B (NF-κB), and mitogen-activated protein kinase signaling pathways; these signaling events regulate cytokine expression and suggest roles for chIL-34 in innate and adaptive immunity. View Full-Text
Keywords: cytokines; chicken; interleukin-34; CSF-1R; signaling pathway cytokines; chicken; interleukin-34; CSF-1R; signaling pathway
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Truong, A.D.; Hong, Y.; Lee, J.; Lee, K.; Kil, D.Y.; Lillehoj, H.S.; Hong, Y.H. Interleukin-34 Regulates Th1 and Th17 Cytokine Production by Activating Multiple Signaling Pathways through CSF-1R in Chicken Cell Lines. Int. J. Mol. Sci. 2018, 19, 1665.

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