Related Experiment Video
Updated: Aug 15, 2026
Characterization of Thymus-dependent and Thymus-independent Immunoglobulin Isotype Responses in Mice Using Enzyme-linked Immunosorbent Assay
Published on: September 7, 2018
Attenuation of Th1 response in decoy receptor 3 transgenic mice
Tsui-Ling Hsu1, Ying-Yu Wu, Yung-Chi Chang
1Institute of Microbiology and Immunology, National Yang-Ming University, Shih-Pai, Taipei, Taiwan.
Abstract:
The soluble decoy receptor 3 (DcR3) is a member of the TNFR superfamily. Because DcR3 is up-regulated in tumor tissues and is detectable in the sera of cancer patients, it is regarded as an immunosuppressor to down-regulate immune responses. To understand the function of DcR3 in vivo, we generated transgenic mice overexpressing DcR3 systemically. In comparison with HNT-TCR (HNT) transgenic mice, up-regulation of IL-4 and IL-10 and down-regulation of IFN-gamma, IL-12, and TNF-alpha were observed in the influenza hemagglutinin(126-138) peptide-stimulated splenocytes of HNT-DcR3 double-transgenic mice. When infected with Listeria monocytogenes, DcR3 transgenic mice show attenuated expression of IFN-gamma as well as increased susceptibility to infection. The Th2 cell-biased phenotype in DcR3 transgenic mice is attributed to decreased IL-2 secretion by T cells, resulting in the suppression of IL-2 dependent CD4(+) T cell proliferation. This suggests that DcR3 might help tumor growth by attenuating the Th1 response and suppressing cell-mediated immunity.
Insights
Soluble decoy receptor 3 (DcR3) suppresses immune responses by promoting Th2 cell bias and reducing T cell proliferation. This suggests DcR3 may aid tumor growth by weakening cell-mediated immunity.
Area of Science:
- Immunology
- Cancer Biology
- Molecular Biology
Background:
- Soluble decoy receptor 3 (DcR3), a TNFR superfamily member, is upregulated in tumors and detectable in cancer patient sera.
- DcR3 is recognized as an immunosuppressor that downregulates immune responses.
Purpose of the Study:
- To investigate the in vivo function of DcR3.
- To generate and analyze transgenic mice with systemic DcR3 overexpression.
Main Methods:
- Generation of HNT-DcR3 double-transgenic mice overexpressing DcR3.
- Analysis of cytokine profiles (IL-4, IL-10, IFN-gamma, IL-12, TNF-alpha) in stimulated splenocytes.
- Infection of DcR3 transgenic mice with Listeria monocytogenes.
- Assessment of T cell proliferation and cytokine secretion.
Main Results:
- DcR3 overexpression led to increased IL-4 and IL-10, and decreased IFN-gamma, IL-12, and TNF-alpha in stimulated splenocytes.
- DcR3 transgenic mice exhibited attenuated IFN-gamma expression and increased susceptibility to Listeria monocytogenes infection.
- A Th2 cell-biased phenotype was observed, linked to reduced IL-2 secretion and suppressed IL-2 dependent CD4(+) T cell proliferation.
Conclusions:
- DcR3 induces a Th2-skewed immune response by suppressing Th1 cytokines and IL-2 production.
- DcR3 may promote tumor growth by attenuating Th1 responses and suppressing cell-mediated immunity.
