Dendritic cells transduced with lentiviral vector targeting RelB gene using RNA interference induce hyporesponsiveness in memory CD4+ T cells and naïve CD4+ T cells

Luo, Lei; Li, Chengwen; Wu, Wei; Lü, Jun; Shan, Juan; Li, Shengfu; Long, Dan; Guo, Yingjia; Li, Feng; Li, Youping

doi:10.1016/j.cellimm.2011.11.001

Cited by 7 publications

(2 citation statements)

References 44 publications

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“…35,36 Lipopolysaccharide has also been suggested to be essential for the regulatory function and migratory capability of these DCs. 37 In accordance with previous reports on the effect of RelB-shRNA DCs on co-cultured T cells, 38 we found that MRL/MpJ RelB-shRNA DCs can induce hyporesponsiveness in both MRL/MpJ and MRL/lpr splenic T cells. These DCs attenuated T-cell proliferation, down-regulated IFN-c expression and induced IL-10-producing splenic CD4 + T lymphocytes from MRL/MpJ mice.…”

Section: Discussionsupporting

confidence: 92%

Rel B‐modified dendritic cells possess tolerogenic phenotype and functions on lupus splenic lymphocytes in vitro

Chan

et al. 2016

Immunology

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SummarySystemic lupus erythematosus (SLE) is an autoimmune disease that is characterized by high morbidity and mortality and its treatment remains challenging. Dendritic cells (DCs) have been shown to participate in the initiation and perpetuation of lupus pathogenesis and the DCs that can induce tolerogenicity appear as potential cell‐based therapy in this condition. In this study, we examined the in vitro tolerogenic properties of bone‐marrow derived DCs (BMDCs) in the murine lupus setting. We used lentiviral transduction of RelB‐silencing short hairpin RNA to modify the expression of RelB, a key transcription factor regulating DC maturation, in BMDCs from MRL/MpJ mice. Tolerogenic properties of RelB‐modified DCs were compared with scrambled control (SC) ‐modified DCs. RelB expression was found to be significantly reduced in RelB‐modified DCs derived from MRL/MpJ mice, wild‐type of the same genetic background as MRL/lpr lupus‐prone mice. These MRL/MpJ RelB‐modified DCs displayed semi‐mature phenotype with expression of lower levels of co‐stimulatory molecules compared with SC‐modified DCs. RelB‐modified DCs were found to be low producers of interleukin‐12p70 (IL‐12p70) and could induce hyporesponsiveness of splenic T cells from MRL/MpJ and MRL/lpr mice. Furthermore, they down‐regulated interferon‐γ expression and induced IL‐10‐producing T cells in MRL/MpJ splenocytes, and attenuated interferon‐γ and IL‐17 expression in MRL/lpr splenic CD4+ lymphocytes. Splenocytes primed by RelB‐modified DCs demonstrated antigen‐specific suppressive effects on allogeneic splenocytes. In conclusion, RelB‐silencing in DCs generates DCs of tolerogenic properties with immunomodulatory function and appears as potential option of cell‐targeted therapy.

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Section: Discussionsupporting

confidence: 92%

Rel B‐modified dendritic cells possess tolerogenic phenotype and functions on lupus splenic lymphocytes in vitro

Chan

et al. 2016

Immunology

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“…Total cell lysates and western blot analysis were performed as previously described (Luo et al, 2012). The antibodies used were the following: anti-phospho-p70S6K, anti-phospho-S6, antiphospho-STAT5 (Tyr694), and anti-phospho-4E-BP-1 (all from Cell Signaling Technology, Beverly, MA); anti-Pim-2 (EPR6987; Epitomics, Burlingame, CA); and anti-FoxP3 (150D/E4; eBioscience, San Diego, CA).…”

Section: Western Blot Analysismentioning

confidence: 99%

Interplay between mTOR and STAT5 signaling modulates the balance between regulatory and effective T cells

Shan¹,

Li²,

Sun³

et al. 2015

Immunobiology

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Effects of tolerogenic dendritic cells generated by siRNA-mediated RelB silencing on immune defense and surveillance functions of T cells

Luo

Sun

Qian

et al. 2013

Cellular Immunology

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Dendritic cells transduced with lentiviral vector targeting RelB gene using RNA interference induce hyporesponsiveness in memory CD4+ T cells and naïve CD4+ T cells

Cited by 7 publications

References 44 publications

Rel B‐modified dendritic cells possess tolerogenic phenotype and functions on lupus splenic lymphocytes in vitro

Rel B‐modified dendritic cells possess tolerogenic phenotype and functions on lupus splenic lymphocytes in vitro

Interplay between mTOR and STAT5 signaling modulates the balance between regulatory and effective T cells

Effects of tolerogenic dendritic cells generated by siRNA-mediated RelB silencing on immune defense and surveillance functions of T cells

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