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Published on: April 8, 2016
Biochemical and morphological characterization of vascular and lymphocytic interleukin-4 receptors
B Schnyder1, S M Lugli, S Schnyder-Candrian
1Institute of Toxicology, Swiss Federal Institute of Technology-ETH, Schwerzenbach, Switzerland.
Insights
The interleukin-4 receptor (IL-4 receptor) is present on lymphocytes and blood vessels, influencing immune responses. This vascular IL-4 receptor, potentially a type II receptor, may play a role in inflammatory events.
Area of Science:
- Immunology
- Cell Biology
- Molecular Biology
Background:
- Interleukin-4 (IL-4) is a key cytokine in immune regulation and allergic inflammation.
- Understanding the distribution and function of the IL-4 receptor is crucial for elucidating IL-4-mediated biological processes.
Purpose of the Study:
- To investigate the tissue distribution of the IL-4 receptor in humans and marmosets.
- To explore the functional implications of IL-4 receptor expression on vascular cells and lymphocytes.
Main Methods:
- Immunofluorescence and flow cytometry were used to detect IL-4 receptor expression.
- Monoclonal antibodies specific for the human IL-4 receptor were employed.
- VCAM-1 upregulation was assessed in vascular cell cultures upon IL-4 stimulation.
Main Results:
- IL-4 receptor positivity was confirmed on lymphocytes (primarily T cells) and vascular cells (smooth muscle and endothelial cells).
- IL-4 induced VCAM-1 upregulation in vascular cells in a genistein-sensitive manner.
- A 65-75 kDa accessory receptor subunit, associated with the IL-13 receptor, was identified with the IL-4 receptor on vascular cells.
Conclusions:
- The IL-4 receptor is expressed on both lymphocytes and vascular tissues.
- A distinct IL-4 receptor complex (type II IL-4 receptor) on vascular cells suggests a role in vascular functional alterations during inflammation.
- These findings highlight the potential importance of vascular IL-4 receptor signaling in immunological and allergic inflammatory responses.
Abstract:
The distribution of the interleukin (IL)-4 receptor in normal human and common marmoset (Callithrix jacchus) tissues was examined by immunofluorescence and flow cytometry using monoclonal antibodies specific for the human IL-4 receptor to gain further insight into IL-4-mediated inflammatory and immunological events. IL-4 receptor positivity was unequivocally demonstrated on lymphocytes, predominantly T cells, and on blood vessels in many tissues. Vascular IL-4 receptor immunofluorescence consisted of a strong smooth muscle cell positivity and weaker positive staining of capillary and venular endothelial cells. Subnanomolar concentrations of IL-4 induced a genistein-sensitive up-regulation of VCAM-1 in vascular cell cultures. Tumor necrosis factor-alpha induced a genistein-resistant up-regulation of VCAM-1. IL-4 strongly induced expression of the IL-4 receptor on splenocytes (T lymphocytes) but not on vascular smooth muscle or endothelial cell cultures. Receptor cross-linking to [125I]IL-4 revealed a 65- to 75-kDa accessory receptor subunit consistent with a recently cloned IL-13 receptor associated with the IL-4 receptor on both vascular endothelial and smooth muscle cells. The demonstration of a vascular distribution pattern for the IL-4 receptor in addition to expression on lymphocytes suggests that vascular functional alterations, transduced through a unique IL-4 receptor complex (the type II IL-4 receptor), may be of importance during immunological and allergic inflammatory events.
