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Concurrent CCR7 Overexpression and RelB Knockdown in Immature Dendritic Cells Induces Immune Tolerance and Improves Skin-Graft Survival in a Murine Model.
- Source :
-
Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology [Cell Physiol Biochem] 2017; Vol. 42 (2), pp. 455-468. Date of Electronic Publication: 2017 Jun 05. - Publication Year :
- 2017
-
Abstract
- Background/aims: Skin transplantation aims to cover skin defects but often fails due to immune rejection of the transplantated tissue. Immature dendritic cells (imDCs) induce immune tolerance but have a low migration rate. After stimulation, imDCs transform into mature DCs, which activate immune rejection. Thus, inducing imDC to obtain a high migration counteracts development of immune tolerance.<br />Methods & Results: We transfected imDCs with a recombinant adenovirus carrying the CCR7 gene (Ad-CCR7) and a small interfering RNA targeting RelB (RelB-siRNA) to concurrently overexpress CCR7 and downregulate RelB expression. Functionally, such cells showed a significantly enhanced migration rate in the chemotactic assay and decreased T-cell proliferation after lipopolysaccharide stimulation in mixed lymphocyte reactions. Cotransfected cells showed an increased ability to induce immune tolerance by upregulating T regulatory (Treg) cells and shifting the Th1/Th2 ratio. Cotransfection of Ad-CCR7 and RelB-siRNA endowed imDCs with resistance to apoptosis and cell death. CCR7 overexpression and RelB knockdown (KD) in imDCs improve skin-graft survival in a murine skin-transplantation model.<br />Conclusion: Transfection with Ad-CCR7 and RelB KD in imDCs may be an effective approach inducing immune tolerance, thus being potentially valuable for inhibiting allograft rejection.<br /> (© 2017 The Author(s). Published by S. Karger AG, Basel.)
- Subjects :
- Adenoviridae
Animals
Dendritic Cells immunology
Dendritic Cells metabolism
Gene Expression Regulation
Graft Rejection genetics
Graft Rejection immunology
Graft Survival genetics
Humans
Mice
Receptors, CCR7 genetics
Skin metabolism
T-Lymphocytes, Regulatory immunology
T-Lymphocytes, Regulatory metabolism
Transfection
Immune Tolerance genetics
Receptors, CCR7 biosynthesis
Skin immunology
Transcription Factor RelB genetics
Subjects
Details
- Language :
- English
- ISSN :
- 1421-9778
- Volume :
- 42
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology
- Publication Type :
- Academic Journal
- Accession number :
- 28578354
- Full Text :
- https://doi.org/10.1159/000477593