Dendritic cells genetically engineered to express IL-4 exhibit enhanced IL-12p70 production in response to CD40 ligation and accelerate organ allograft rejection

Kaneko, Katsuhiko; Wang, Z.; Kim, S. H.; Morelli, Adrián E.; Robbins, Paul D.; Thomson, Angus W.

doi:10.1038/sj.gt.3301872

Cited by 24 publications

(11 citation statements)

References 47 publications

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“…However, the combination of immune injury compounded by the direct effects of IL-4 on the liver cannot be excluded. Finally, IL-4 might be promoting liver transplant rejection through its ability to activate dendritic cells to increase IL-12 expression, which promotes rejection (27).…”

Section: Discussionmentioning

confidence: 99%

Posttransplant Interleukin-4 Treatment Converts Rat Liver Allograft Tolerance to Rejection

Wang

Li²,

Cordoba³

et al. 2005

Transplantation

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IL-4, a T-helper type 2 cytokine that has previously been shown to inhibit delayed-type hypersensitivity responses such as rejection, was found to promote rejection of liver allografts. There was only slight evidence of a graft-specific antibody response, showing that IL-4 induces liver allograft rejection in association with some, but not all, of the changes accompanying rejection in the PVG-->Lewis strain combination.

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Section: Discussionmentioning

confidence: 99%

Posttransplant Interleukin-4 Treatment Converts Rat Liver Allograft Tolerance to Rejection

Wang

Li²,

Cordoba³

et al. 2005

Transplantation

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“…On the other hand, the presence of allergen sensitization in a CD4-deficient patient in this cohort is worth noting. We believe that IL4/IL13 could be produced by innate cells like natural killer (NK) cells, NKT cells, or dendritic cells as has previously been published [15,16].…”

Section: Discussionmentioning

confidence: 99%

Sensitization to Aeroallergens in Patients with Primary Immunodeficiencies

Segundo¹,

Canabrava²

2018

Int Arch Allergy Immunol

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Background: Primary immunodeficiencies (PID) are a heterogeneous group of diseases that cause alterations in the immune system, leading to the increased susceptibility to infections, autoimmune diseases, and malignancies. The aim was to evaluate the presence of clinical manifestations and diagnoses of asthma, rhinitis, and atopic dermatitis in patients diagnosed with PID, and correlate these with allergen sensitization verified by skin prick testing (SPT). Material and Methods: This cross-sectional, descriptive, and observational study was conducted from February 2015 to February 2016. We performed a medical report analysis and SPT for aeroallergens in patients with a PID diagnosis. Results: Thirty-one patients with a PID diagnosis were included. The mean age of the participants was 15.41 years. From the 31 patients, 28 had symptoms suggestive of allergic disease (asthma, rhinitis, and atopic dermatitis) and only 7 presented positive SPT for at least 1 aeroallergen. Conclusion: The frequency of allergenic sensitization in the group of patients with PID and symptoms suggestive of asthma, rhinitis, or atopic dermatitis is lower than that found in the general population, probably due the impairment of IgE formation secondary to their immunologic alterations.

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“…Localized IL-10 gene transfer mediated by adenovirus or liposome has been the most effective gene therapy, other than CTLA4Ig, for prolonging allograft survival in various animal models (4,13,14); however, true tolerance was never achieved (15,16). IL-4 shares many of its activities with IL-10, and some activities with IL-13; however, unexpectedly, the observations of its role as a mediator of allograft rejection are inconsistent (17,18).…”

mentioning

confidence: 99%

Liposome-Mediated Combinatorial Cytokine Gene Therapy Induces Localized Synergistic Immunosuppression and Promotes Long-Term Survival of Cardiac Allografts

Furukawa¹,

Oshima²,

Tung³

et al. 2005

The Journal of Immunology

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Localized gene transfer has the potential to introduce immunosuppressive molecules only into the transplanted allograft, which would limit systemic side effects, and prolong allograft survival. However, an applicable gene transfer strategy is not available, and the feasible therapeutic gene(s) has not yet been determined. We developed an ex vivo liposome-mediated gene therapy strategy that is able to intracoronary deliver the combination of IL-4 and IL-10 cDNA expression vectors to the allograft simultaneously. We examined the efficiency, efficacy, and cardiac adverse effects of this combinatorial gene therapy protocol using a rabbit functional cervical heterotopic heart transplant model. Although the efficiency was moderate, the expression of both transgenes was long lasting and localized only in the target organ. The mean survival of cardiac allograft was prolonged from 7 to >100 days. Synergism of overexpressed IL-4 and IL-10 in the inhibition of T lymphocyte infiltration and cytoxicity, and modulation of Th1/Th2 cytokine production promote long-term survival of cardiac allografts.

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Dendritic cells genetically engineered to express IL-4 exhibit enhanced IL-12p70 production in response to CD40 ligation and accelerate organ allograft rejection

Cited by 24 publications

References 47 publications

Posttransplant Interleukin-4 Treatment Converts Rat Liver Allograft Tolerance to Rejection

Posttransplant Interleukin-4 Treatment Converts Rat Liver Allograft Tolerance to Rejection

Sensitization to Aeroallergens in Patients with Primary Immunodeficiencies

Liposome-Mediated Combinatorial Cytokine Gene Therapy Induces Localized Synergistic Immunosuppression and Promotes Long-Term Survival of Cardiac Allografts

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