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Published on: July 11, 2015
Modulation of human immune responses by bovine interleukin-10
Gerco den Hartog1, Huub F J Savelkoul, Ruud Schoemaker
1Cell Biology and Immunology Group, Wageningen University, Wageningen, The Netherlands.
Insights
Bovine interleukin-10 (IL-10) effectively suppresses human immune cell activation, indicating potential applications in infant nutrition and inflammatory disease prevention.
Area of Science:
- Immunology
- Cell Biology
- Comparative Medicine
Background:
- Cytokines can exhibit cross-species functionality.
- Bovine interleukin-10 (IL-10) shares significant sequence identity (76.8%) with human IL-10.
Purpose of the Study:
- To investigate the immunomodulatory effects of bovine IL-10 on human monocytes and dendritic cells.
- To determine if bovine IL-10 can inhibit Toll-like receptor (TLR)-induced activation pathways in human myeloid cells.
Main Methods:
- Isolation of peripheral blood monocytes from healthy donors.
- Differentiation of monocytes into dendritic cells (DCs) using IL-4 and GM-CSF.
- Treatment with recombinant bovine IL-10 and assessment of TLR-induced activation, using blocking antibodies to confirm receptor binding.
Main Results:
- Recombinant bovine IL-10 demonstrated dose-dependent inhibition of TLR-induced monocyte and monocyte-derived DC activation.
- The inhibitory effect of bovine IL-10 on human monocytes was confirmed to be mediated through binding to the human IL-10 receptor.
- Bovine IL-10 potently inhibited human myeloid cell activation.
Conclusions:
- Bovine IL-10 possesses significant immunomodulatory activity on human myeloid cells.
- This cross-species activity suggests potential therapeutic applications for bovine IL-10 in preventing inflammatory conditions like necrotizing enterocolitis and allergies.
- Bovine IL-10 may be beneficial in infant foods and immunomodulatory diets to enhance mucosal tolerance and reduce intestinal inflammation.
Abstract:
Cytokines can be functionally active across species barriers. Bovine IL-10 has an amino acid sequence identity with human IL-10 of 76.8%. Therefore, the aim of this study was to evaluate whether bovine IL-10 has immunomodulatory activities on human monocytes and dendritic cells. Peripheral blood monocytes were isolated from healthy donors, and used directly or allowed to differentiate to dendritic cells under the influence of IL-4 and GM-CSF. Recombinant bovine IL-10 inhibited TLR induced activation of monocytes, and dose-dependently inhibited LPS-induced activation of monocyte-derived DCs comparable to human IL-10. By using blocking antibodies to either bovine IL-10 or the human IL-10 receptor it was demonstrated that inhibition of monocyte activation by bovine IL-10 was dependent on binding of bovine IL-10 to the human IL-10R. These data demonstrate that bovine IL-10 potently inhibits the activation of human myeloid cells in response to TLR activation. Bovine IL-10 present in dairy products may thus potentially contribute to the prevention of necrotizing enterocolitis and allergy, enhance mucosal tolerance induction and decrease intestinal inflammation and may therefore be applicable in infant foods and in immunomodulatory diets.
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